Direct renin inhibition in chronic kidney disease

DEFF Research Database (Denmark)

Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik

2013-01-01

that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need....... In addition, combination treatment seemed safe and effective also in patients with impaired kidney function. These initial findings formed the basis for the design of a large morbidity and mortality trial investigating aliskiren as add-on to standard treatment. The study has just concluded, but was terminated...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...

Active immunization against renin in normotensive marmoset

International Nuclear Information System (INIS)

Michel, J.B.; Guettier, C.; Philippe, M.; Galen, F.X.; Corvol, P.; Menard, J.

1987-01-01

Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Callithrix jacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutneous injections of 30 μg each, with complete and then incomplete Freund's adjuvant. Three marmosets were injected with adjuvant only and served as controls. Blood sampling and blood pressure measurements were performed weekly. After the third injection, the five marmosets immunized against renin developed a high titer of renin antibodies (50% binding of 125 I-labeled human renin at a dilution of ≥ 1:10,000). The antibodies inhibited the enzymatic activity of both marmoset and human renins. At the same time, systolic blood pressure decreased significantly. Plasma renin enzyme activity was undetectable in the animals. Plasma aldosterone decreased significantly. After 1-4 months with low blood pressure, a normal urinary output, and a normal plasma creatinine, the five marmosets became sick and died within one month. At autopsy an immunological renal disease, characterize by the presence of immunoglobulin and macrophage infiltration colocalized with renin, was found. No immunoglobulin was detectable in extrarenal vessels or in other organs. These experiments demonstrate that, in this primate, a chronic blockade of the renin-angiotensin system can be achieved by active immunization against homologous renin, but this blockade is associated with the development of an autoimmune disease localized in the kidney

Living alone and activation of the renin-angiotensin-aldosterone-system: Differential effects depending on alexithymic personality features.

Science.gov (United States)

Terock, Jan; Hannemann, Anke; Janowitz, Deborah; Völzke, Henry; Nauck, Matthias; Freyberger, Harald-Jürgen; Wallaschofski, Henri; Grabe, Hans Jörgen

2017-05-01

Living alone is considered as a chronic stress factor predicting different health conditions and particularly cardiovascular disease (CVD). Alexithymia is associated with increased psychological distress, less social skills and fewer close relationships, making alexithymic subjects particularly susceptible to chronic stress imposed by "living alone". Only few studies investigated the renin-angiotensin-aldosterone-system (RAAS) activity in response to chronic stress. We aimed at evaluating the effects of "living alone" as a paradigm for chronic stress on RAAS activity and putatively differential effects depending on alexithymic personality features. Alexithymia and serum concentrations of renin and aldosterone were measured in 944 subjects from the population-based SHIP-1 study. Subgroups were formed using the median of the Toronto Alexithymia Scale-20 (TAS-20) and a cohabitation status of "living alone" or "living together". Analyses were adjusted for various psychosocial, behavioral and metabolic risk factors. "Living alone" was associated with elevated plasma renin (p<0.01, β=0.138) but not aldosterone concentrations in the total sample. On subgroup level, we found associations of "living alone" and elevated renin concentrations only in subjects low in TAS-20 scores (p<0.01, β=0.219). Interactional effects of alexithymia×cohabitation status were found for the aldosterone-to-renin ratio (p=0.02, β=-0.234). The association of chronic stress imposed by "living alone" with increased RAAS activity contributes to explain the relationship of this psychosocial stress condition and increased risk for CVD. In contrast, alexithymic subjects may be less affected by the deleterious effects of "living alone". Copyright © 2017 Elsevier Inc. All rights reserved.

Methodologic issues in the measurement of urinary renin

NARCIS (Netherlands)

L.C.W. Roksnoer (Lodi); K. Verdonk (Koen); I.M. Garrelds (Ingrid); J.M. van Gool (Jeanette); R. Zietse (Bob); E.J. Hoorn (Ewout); A.H.J. Danser (Jan)

2014-01-01

textabstractBackground and objectives Alge et al. recently reported that urinary renin may be a prognostic biomarker for AKI after cardiac surgery. However, their urinary renin levels far exceeded published plasma renin levels, whereas normally, urinary renin is,10%of plasma renin. This result

Intracellular renin disrupts chemical communication between heart cells. Pathophysiological implications

Directory of Open Access Journals (Sweden)

Walmor eDe Mello

2015-01-01

Full Text Available The influence of intracellular renin on the process of chemical communication between cardiac cells was investigated in cell pairs isolated from the left ventricle of adult Wistar Kyoto rats. The enzyme together with Lucifer yellow CH was dialyzed into one cell of the pair using the whole cell clamp technique. The diffusion of the dye in the dialyzed and in non-dialyzed cell was followed by measuring the intensity of fluorescence in both cells as a function of time. The results indicated that; 1 under normal conditions, Lucifer Yellow flows from cell-to-cell through gap junctions; 2 the intracellular dialysis of renin (100nM disrupts chemical communication-an effect enhanced by simultaneous administration of angiotensinogen (100nM; 3 enalaprilat (10-9M administered to the cytosol together with renin reduced drastically the uncoupling action of the enzyme; 4 aliskiren (10-8M inhibited the effect of renin on chemical communication;5 the possible role of intracellular renin independently of angiotensin II (Ang II was evaluated including the increase of the inward calcium current elicited by the enzyme and the possible role of oxidative stress on the disruption of cell communication; 6 the possible harmful versus the beneficial effect of intracellular renin during myocardial infarction was discussed;7 the present results indicate that intracellular renin due to internalization or in situ synthesis, causes a severe impairment of chemical communication in the heart resulting in derangement of metabolic cooperation with serious consequences for heart function.

Influence of bicarbonate on the sensitivity of renin release to sodium chloride

DEFF Research Database (Denmark)

Skøtt, O; Jensen, B L

1989-01-01

glomeruli treated with bicarbonate/chloride exchange inhibitor (DNDS), NaCl/KCl cotransport inhibitor (bumetanide), or Na+/H+ antiport inhibitor (amiloride) in the presence or absence of bicarbonate. In addition, the sensitivity to increases in osmolality by addition of sucrose was tested in the presence...... or absence of bicarbonate. Renin release from time controls superfused with a bicarbonate-free Ringer was identical to release from glomeruli superfused with a bicarbonate Ringer. DNDS (0.11 or 1.1 mM) had no effect on renin release in a bicarbonate Ringer. 30 mM sucrose inhibited renin release independently...... of bicarbonate. 15 mM NaCl stimulated renin release when bicarbonate was absent, while it caused an inhibition in the presence of bicarbonate. When bicarbonate/chloride exchange was inhibited, addition of NaCl stimulated renin release even when bicarbonate was present. The effect of NaCl on renin release...

Studies on renin release in vitro

DEFF Research Database (Denmark)

Skøtt, O

1989-01-01

1) Measurements of renin secretion from single arterioles at time intervals down to 20 seconds showed that the renin secretion is episodic, the amount of renin released during each episode corresponding to the estimated content of one secretory granule. 2) A decrease in osmolality elicits episodi...

Renin secretion from permeabilized juxtaglomerular cells requires a permeant cation

DEFF Research Database (Denmark)

Jensen, B L; Ellekvist, Peter; Skøtt, O

1999-01-01

The cytosolic concentration of chloride correlates directly with renin secretion from renal juxtaglomerular granular (JG) cells. In the present study, the mechanism by which chloride stimulates renin release was investigated in a preparation of permeabilized rat glomeruli with attached JG cells....... An isosmotic increase in the concentration of chloride by 129 mM stimulated renin release 16- to 20-fold. Substitution of K+ by the impermeant cation N-methyl-d-glucamine (NMDG) abolished this response, while substitution with Na+ caused marginal inhibition. Substitution with Cs+ had no effect. Addition...... of sucrose, which permeates the secretory granules poorly, also abolished the stimulation of renin secretion by KCl. The response to KCl was not affected by K+-channel antagonists or by agonists of K+ channels. Chloride channel blockers were also without effect on the secretory response to KCl. When the ATP...

Influence of Aging on Plasma Renin Activity

International Nuclear Information System (INIS)

Cho, K. W.; Kim, S. H.; Kang, S. K.; Choi, H. Y.

1982-01-01

Influence of aging on plasma renin activity was evaluated in healthy normotensive subjects(age range 21-63 years, 413 males) devoid of cardiorenal or endocrinological problems. The age-related decrease of plasma renin activity in the subjects between 21-28 years group and 36-42 years group was slight, but over the 43 years groups was significantly different. The age-related suppression of plasma renin activity was much more smooth and continuous all over the age ranges evaluated. The sexual difference in plasma renin activity was noticed between the subjects of 22 years old group (34 males) and 19 years group (34 females) (p<0.003). The data suggest that the age-related suppression of plasma renin activity appeared in healthy normotensive subjects should be considered in the case of evaluation of low renin essential hypertension.

Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

Energy Technology Data Exchange (ETDEWEB)

Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S. [Korea Atomic Emergy Research Institute, Seoul (Korea, Republic of)

1973-03-15

The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

International Nuclear Information System (INIS)

Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S.

1973-01-01

The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

Therapeutic vaccines against human and rat renin in spontaneously hypertensive rats.

Directory of Open Access Journals (Sweden)

Zhihua Qiu

Full Text Available Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. As the initiation factor of renin-angiotensin system, renin plays a critical role in hypertension. In this study, we selected six peptides (rR32, rR72, rR215, hR32, hR72, and hR215 belonging to potential epitopes of rat and human renin. The main criteria were as follows: (1 include one of renin catalytic sites or the flap sequence; (2 low/no-similarity when matched with the host proteome; (3 ideal antigenicity and hydrophilicity. The peptides were coupled to keyhole limpet hemocyanin and injected into SpragueDawley (SD rats, spontaneously hypertensive rats (SHRs and Wistar-Kyoto rats. The antisera titers and the binding capacity with renin were detected. The effects of the anti-peptides antibodies on plasma renin activity (PRA and blood pressure were also determined. All peptides elicited strong antibody responses. The antisera titers ranged from 1:32,000 to 1:80,000 in SD rats on day 63. All antisera could bind to renin in vitro. Compared with the control antibody, the antibodies against the rR32, hR32, rR72 and hR72 peptides inhibited PRA level by up to about 50%. Complete cross-reactivity of the anti-rR32 antibody and the anti-hR32 antibody was confirmed. The epitopes rR32 and hR32 vaccines significantly decreased systolic blood pressure (SBP of SHRs up to 15mmHg (175±2 vesus 190±3 mmHg, P = 0.035; 180±2 vesus 195±3 mmHg, P = 0.039, while no obvious effect on SD rats. Additionally, no significant immune-mediated damage was detected in the vaccinated animals. In conclusion, the antigenic peptide hR32 vaccine mimicking the (32Asp catalytic site of human renin may constitute a novel tool for the development of a renin vaccine.

Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction

DEFF Research Database (Denmark)

Solomon, Scott D; Shin, Sung Hee; Shah, Amil

2011-01-01

Direct renin inhibitors provide an alternative approach to inhibiting the renin-angiotensin-aldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following...

Comparative biochemistry of renins and angiotensins in the vertebrates.

Science.gov (United States)

Nakajima, T; Khosla, M C; Sakakibara, S

1978-09-01

Comparative biochemistry of renins and angiotensins was discussed. Renin extracted from hog kidney was different from that from mouse submaxillary glands in immunoreactivity and carbohydrate content. Rat kidney renin was also different from hog kidney renin in the amino acid composition. The presence of big and big-big renins was pointed out immunochemically. These big renins were considered to be precursors of kidney renin. Angiotensins in mammalian and nonmammalian species produced by renal or extrarenal renin have been differentiated by some biochemical and pharmacological criteria. Some of these angiotensins were analyzed sequentially. The replacements of amino acid residues at positions 1, 5, and/or 9 of angiotensin I have been demonstrated in nonmammalian species. Specific pressor activities have been determined using synthetic angiotensins by a 4 point assay in rat. Specific pressor activities of various angiotensins were obtained from the dose-blood pressure-response curves using a single angiotensin sample per assay rat.

The Improvement of Hypertension by Probiotics: Effects on Cholesterol, Diabetes, Renin, and Phytoestrogens

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Huey-Shi Lye

2009-08-01

Full Text Available Probiotics are live organisms that are primarily used to improve gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, lactose intolerance, and to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects beyond gastrointestinal health, as they were found to improve certain metabolic disorders such as hypertension. Hypertension is caused by various factors and the predominant causes include an increase in cholesterol levels, incidence of diabetes, inconsistent modulation of renin and imbalanced sexual hormones. This review discusses the antihypertensive roles of probiotics via the improvement and/or treatment of lipid profiles, modulation of insulin resistance and sensitivity, the modulation of renin levels and also the conversion of bioactive phytoestrogens as an alternative replacement of sexual hormones such as estrogen and progesterone.

Plasma renin activity profile in normal and hypertensive Filipinos

International Nuclear Information System (INIS)

Guevara, R.; Torres, J. Jr.; Abundo, H.P.; Perez, A.P.

To establish a base line profile of plasma renin activity in normotensive and hypertensive Filipinos, 1.019 cases, 479 males and 540 females with an age range 14 - 89 years (mean - 46 + -20) were studied at the Santo Tomas University Hospital of various life styles from the Metro-Manila area, 248 comprised the normotensive group (male - 122 or 49.2 %, female 126 or 50.8 %) and 771 were hypertensive. Of these, 711 (92.6 %) has essential hypertension and are presented in this report. Plasma Renin Activity was determined by radioimmunoassay using Dainabot Renin-Ricket. Concurrent 24 hr. urine sodium and potassium were determined. Nomograms of plasma renin activity as related to urine sodium excretion were drawn after computerized statistical analysis of data. The normal mean value of plasma renin activity was found to be 1.64 + - 0.81 ng./ml./hr. in the upright position and 1.15 + - .68 ng./ml./hr. in the supine position. Based on the nomogram derived, the values obtained in the 711 cases of essential hypertension were classified into High Renin - 14.3 % Normal Renin - 56.1 % and Low Renin - 29.6 %. This study establishes normal levels of plasma renin activity as well as define and classify same renin activity among hypertensive Filipinos, a useful and practicable guide for treatment and can be of prognostic significance. (author)

Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis

DEFF Research Database (Denmark)

Schneider, Markus; Hua, Tsushung A; Böhm, Michael

2010-01-01

The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective.......The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective....

Urinary renin and angiotensinogen in type 2 diabetes

DEFF Research Database (Denmark)

Persson, Frederik; Lu, Xifeng; Rossing, Peter

2013-01-01

Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade.......Urinary levels of renin-angiotensin-aldosterone system (RAAS) components may reflect renal RAAS activity and/or the renal efficacy of RAAS inhibition. Our aim was to determine whether urinary angiotensinogen and renin are circulating RAAS-independent markers during RAAS blockade....

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone study

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McInnes Gordon T

2007-05-01

Full Text Available Abstract Background High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT1study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study. The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting. Methods/design The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios. Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios. Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement

The Renal Renin-Angiotensin System

Science.gov (United States)

Harrison-Bernard, Lisa M.

2009-01-01

The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and…

Effect of Dual Blockade of Renin-Angiotensin Aldosterone System ...

African Journals Online (AJOL)

Methods: Patients with diabetes of > 5 years duration, proteinuria at a ... nephropathy, Azotemia, Proteinuria, Aldosterone, Renin, Blood pressure ... Hypertension is a risk factor that exacerbates all ... Arterial tension values of the patients were measured with an. ERKA sleeve .... receiving treatment remained within normal.

Bovine ovarian cells have (pro)renin receptors and prorenin induces resumption of meiosis in vitro.

Science.gov (United States)

Dau, Andressa Minussi Pereira; da Silva, Eduardo Pradebon; da Rosa, Paulo Roberto Antunes; Bastiani, Felipe Tusi; Gutierrez, Karina; Ilha, Gustavo Freitas; Comim, Fabio Vasconcellos; Gonçalves, Paulo Bayard Dias

2016-07-01

The discovery of a receptor that binds prorenin and renin in human endothelial and mesangial cells highlights the possible effect of renin-independent prorenin in the resumption of meiosis in oocytes that was postulated in the 1980s.This study aimed to identify the (pro)renin receptor in the ovary and to assess the effect of prorenin on meiotic resumption. The (pro)renin receptor protein was detected in bovine cumulus-oocyte complexes, theca cells, granulosa cells, and in the corpus luteum. Abundant (pro)renin receptor messenger ribonucleic acid (mRNA) was detected in the oocytes and cumulus cells, while prorenin mRNA was identified in the cumulus cells only. Prorenin at concentrations of 10(-10), 10(-9), and 10(-8)M incubated with oocytes co-cultured with follicular hemisections for 15h caused the resumption of oocyte meiosis. Aliskiren, which inhibits free renin and receptor-bound renin/prorenin, at concentrations of 10(-7), 10(-5), and 10(-3)M blocked this effect (Pmeiosis resumption, cumulus-oocyte complexes and follicular hemisections were treated with prorenin and with angiotensin II or saralasin (angiotensin II antagonist). Prorenin induced the resumption of meiosis independently of angiotensin II. Furthermore, cumulus-oocyte complexes cultured with forskolin (200μM) and treated with prorenin and aliskiren did not exhibit a prorenin-induced resumption of meiosis (Pmeiosis in cattle. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of human renin expression in chorion cell primary cultures

International Nuclear Information System (INIS)

Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L.

1990-01-01

The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3 endash to 6 endash fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'endash flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'endash flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter

On the origin of urinary renin: A translational approach

NARCIS (Netherlands)

L.C.W. Roksnoer (Lodi); Heijnen, B.F.J. (Bart F.J.); Nakano, D. (Daisuke); Peti-Peterdi, J. (Janos); S.B. Walsh (Stephen); I.M. Garrelds (Ingrid); J.M. van Gool (Jeanette); R. Zietse (Bob); H.A.J. Struijker Boudier (Harry A.); E.J. Hoorn (Ewout); A.H.J. Danser (Jan)

2016-01-01

textabstractUrinary angiotensinogen excretion parallels albumin excretion, which is not the case for renin, while renin's precursor, prorenin, is undetectable in urine. We hypothesized that renin and prorenin, given their smaller size, are filtered through the glomerulus in larger amounts than

Active renin mass concentration to determine aldosterone-to-renin ratio in screening for primary aldosteronism

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Corbin F

2011-07-01

Full Text Available François Corbin1, Pierre Douville2, Marcel Lebel3 1Division of Biochemistry, l'Université de Sherbrooke, Sherbrooke, Quebec, Canada; 2Division of Biochemistry; 3Division of Nephrology, L'Hôtel-Dieu de Québec Hospital and l'Université Laval, Quebec, CanadaBackground: Active renin mass concentration (ARC is independent of the endogenous level of angiotensinogen, and less variable and more reproducible than plasma renin activity. Reference values for the aldosterone-to-renin ratio (ARR using ARC are still undefined. The objective of the present study was to determine the threshold of ARR using ARC measurement to screen for primary aldosteronism.Methods: A total of 211 subjects were included in the study, comprising 78 healthy normotensive controls, 95 patients with essential hypertension, and 38 patients with confirmed primary aldosteronism (20 with surgery-confirmed aldosterone-producing adenoma and 18 with idiopathic adrenal hyperplasia. Blood samples were drawn from ambulatory patients and volunteers in the mid-morning without specific dietary restriction for measuring plasma aldosterone concentration, ARC, and serum potassium.Results: Most normotensive controls and essential hypertension patients had ARR results below 100 pmol/ng, a value which corresponded to 3.3 times the median of these two groups.Conclusion: Patients with ARR values above this level should be considered for further investigation (confirmatory tests or for repeat testing should ARR values be borderline. This study indicates that ARC can be used reliably in determining ARR for primary aldosteronism screening.Keywords: primary aldosteronism, active renin mass concentration, aldosterone-to-renin ratio

Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

Science.gov (United States)

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

Renal renin secretion as regulator of body fluid homeostasis

DEFF Research Database (Denmark)

Damkjær, Mads; Isaksson, Gustaf L; Stubbe, Jane

2013-01-01

The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium...

Radioimmunoassay for plasma renin activity

International Nuclear Information System (INIS)

1975-01-01

A radioimmunoassay for the determination of renin activity in blood plasma is described. The plasma sample is mixed with a generator buffer solution also containing an inhibitor for enzymes which convert angiotensin I into other substances. The renin in the plasma sample converts angiotensinogen into angiotensin I. The amount of angiotensin I is then measured with a competitive binding method using 125 I-labelled angiotensin I and antibodies to angiotensin I

Total renin after gonadotropin stimulation in polycystic ovarian disease.

Science.gov (United States)

Matinlauri, I; Anttila, L; Jaatinen, T A; Koskinen, P; Aalto, M; Irjala, K; Nikkanen, V

1995-02-01

To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. The concentrations of total renin in plasma and FF, serum E2, and protein in FF. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Mechanisms of renin release from juxtaglomerular cells

DEFF Research Database (Denmark)

Skøtt, O; Salomonsson, Max; Sellerup Persson, Anja

1991-01-01

In microdissected, nonperfused afferent arterioles changes in intravascular pressure did not affect renin secretion. On the contrary, renin release from isolated afferent arterioles perfused in a free-flow system has been reported to be sensitive to simultaneous changes in luminal pressure and fl....... Hence local blood flow may be involved in the baroreceptor control of renin release. If flow is sensed, the sensor is likely to be located near the endothelial cell layer, where ion channels have been shown to be influenced by variations in shear stress....

The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production

DEFF Research Database (Denmark)

Tinning, Anne Robdrup; Jensen, Boye L; Schweda, Frank

2014-01-01

Processing and release of secretory granules involve water movement across granule membranes. It was hypothesized that the water channel aquaporin-1 (AQP-1) contributes directly to recruitment of renin-positive cells in the afferent arteriole. AQP1(-/-) and (+/+) mice were fed a low NaCl diet (LS...... to baseline with no difference between genotypes. Plasma nitrite/nitrate concentration was unaffected by genotype and LS-ACEI. In AQP1(-/-) mice, the number of afferent arterioles with recruitment was significantly lower compared to (+/+) after LS-ACEI. It is concluded that aquaporin-1 is not necessary...... for acutely stimulated renin secretion in vivo and from isolated perfused kidney, whereas recruitment of renin-positive cells in response to chronic stimulation is attenuated or delayed in AQP1(-/-) mice....

The renin-angiotensin system in kidney development

DEFF Research Database (Denmark)

Jensen, B L; Stubbe, J; Madsen, K

2004-01-01

Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data on the develo......Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data...... on the developmental changes of RAAS and COX-2 and the pathways by which they are activated; their possible interplay and the mechanisms by which they affect kidney development. Intrarenal and circulating renin and angiotensin II (ANG II) are stimulated at birth in most mammals. In rats, renin and ANG II stay...... glucocorticoid concentration and by a low NaCl intake. Studies with selective inhibitors of COX-2 and COX-2 null mice show that COX-2 activity stimulates renin secretion from JG-cells during postnatal kidney development and that lack of COX-2 activity leads to pathological change in cortical architecture...

The role of the renin-angiotensin-aldosterone system in heart failure

Directory of Open Access Journals (Sweden)

Thomas Unger

2004-03-01

Full Text Available Activity of the renin-angiotensin-aldosterone system (RAAS is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation. Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third-generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease. Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II (in addition to angiotensin-converting enzyme [ACE], has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo. Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation. Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.

Inhibition of calcineurin phosphatase promotes exocytosis of renin from juxtaglomerular cells

DEFF Research Database (Denmark)

Madsen, Kirsten; Friis, Ulla Glenert; Gooch, Jennifer L

2010-01-01

. Simultaneous exposure to EGTA and CsA had no additive effect. The protein kinase A (PKA) blocker RpcAMPs had no effect on the CsA-induced increase in membrane capacitance. Intra- and extracellular application of tacrolimus did not alter membrane capacitance. A calmodulin antagonist (calmidazolium) and Cs...... after CsA treatment of the A-alpha knockout, while renin mRNA was suppressed. We conclude that calcineurin and calcium/calmodulin suppress exocytosis of renin from juxtaglomerular cells independent of PKA....

The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension

NARCIS (Netherlands)

van den Born, Bert-Jan H.; Koopmans, Richard P.; van Montfrans, Gert A.

2007-01-01

BACKGROUND: Malignant hypertension is a renin-dependent form of hypertension. However, the variations in renin-angiotensin system (RAS) activation in malignant hypertension are not completely understood. A proposed mechanism for ongoing RAS activation is the presence of microangiopathic hemolysis

Structural adaptation to ischemia in skeletal muscle: effects of blockers of the renin-angiotensin system

NARCIS (Netherlands)

Scheidegger, K. J.; Nelissen-Vrancken, M. H.; Leenders, P. J.; Daemen, M. J.; Smits, J. F.; Wood, J. M.

1997-01-01

To investigate the effects of long-term treatment with blockers of the renin-angiotensin system on capillarization and growth of fibers in ischemic hind-limb muscles and in muscles under normal growth conditions. Ischemia was induced by partial ligation of the left common iliac artery. Ischemia

A Study on Plasma Renin Activity in Essential Hypertension

International Nuclear Information System (INIS)

Choe, Kang Won; Lee, Jung Sang; Cho, Bo Yeon; Koh, Chang Soon; Lee, Mun Ho

1975-01-01

Radioimmunoassay for the measurement of plasma renin activity (PRA) was performed in 43 normal Koreans and 45 patients with essential hypertension. Plasma samples were drawn in supine position in the morning and after upright posture for 4 hours. Urinary sodium excretion rates were measured in the concurrent 24 hour urine samples, an index of their sodium balance. The results were as follows: 1) There was an inverse correlation between 24 hr sodium excretion and PRA. The normal values of PRA in supine position ranged from 1.0 to 7.0 ng/ml/hr. when 24 hour sodium excretion were between 50 to 150 mEq. PRA in elderly tended to be low. 2) When stimulated by 4 hour upright posture, PRA increased by 2.6 times from the baseline value. 3) Of the 45 patients with essential hypertension, PRA was low in 10 cases (22.2%), normal in 28 cases (62.2%), and high in 7 cases (15.6%). 4) In the normal and high renin groups, who tended to be younger in ages, mean diastolic blood pressure and BUN were higher than in low renin group. Though hypertensive retinopathy and left ventricular hypertrophy in ECG were more prevalent in the former, no significant differences were noted as in the case of serum cholesterol. 5) There were 8 cases of cardiovascular complications (7 with cerebral vascular accident, 1 with myocardial infarction); 3 in low renin group (30%), 2 in normal renin (7.1%) and 3 in higher renin group (42.9%). This figure indicated higher rate of cardiovascular complications in higher renin groups, and lower rate in normal renin group. But the incidence of the complication was not significantly low in low renin group.

Renin release

DEFF Research Database (Denmark)

Schweda, Frank; Friis, Ulla; Wagner, Charlotte

2007-01-01

in the walls of renal afferent arterioles at the entrance of the glomerular capillary network. It has been known for a long time that renin synthesis and secretion are stimulated by the sympathetic nerves and the prostaglandins and are inhibited in negative feedback loops by angiotensin II, high blood pressure...

The Protective Arm of the Renin Angiotensin System (RAS)

DEFF Research Database (Denmark)

understanding of the protective side of the Renin Angiotensin System (RAS) involving angiotensin AT2 receptor, ACE2, and Ang(1-7)/Mas receptor Combines the knowledge of editors who pioneered research on the protective renin angiotensin system including; Dr. Thomas Unger, one of the founders of AT2 receptor......The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early insight into a complex system which...... will become of major medical importance in the near future. Focusing on recent research, The Protective Arm of the Renin Angiotensin System presents a host of new experimental studies on specific components of the RAS, namely angiotensin AT2 receptors (AT2R), the angiotensin (1-7) peptide with its receptor...

Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

Science.gov (United States)

Reid, Ian A.

1994-01-01

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

New sensitive direct radioimmunoassay for human plasma renin and its clinical application

International Nuclear Information System (INIS)

Higaki, J.; Ogihara, T.; Imai, N.; Kumahara, Y.; Hontani, S.; Nishiura, M.; Ogawa, H.; Hirose, S.; Murakami, K.

1984-01-01

A new sensitive direct radioimmunoassay for human plasma renin has been developed. Renin was purified from Haas' preparation utilizing a pepstatin-C 6 -Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from this assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation, but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension was not significantly different from values in normal controls. The values were higher in patients with renovascular hypertension, malignant hypertension and Bartter's syndrome, but lower in patients with primary aldosteronism than in normal controls. 20 references, 7 figures

Regulation of renin secretion by renal juxtaglomerular cells

DEFF Research Database (Denmark)

Friis, Ulla G; Madsen, Kirsten; Stubbe, Jane

2013-01-01

A major rate-limiting step in the renin-angiotensin-aldosterone system is the release of active renin from endocrine cells (juxtaglomerular (JG) cells) in the media layer of the afferent glomerular arterioles. The number and distribution of JG cells vary with age and the physiological level...

Anthology of the renin-angiotensin system: a one hundred reference approach to angiotensin II antagonists.

Science.gov (United States)

Ménard, J

1993-04-01

To provide a historical overview of the renin-angiotensin system as a guide to the introduction of a new therapeutic pathway, non-peptide inhibition of a angiotensin II. One hundred references were selected as a personal preference, for their originality or for their potential impact on medicine. This review raises the following questions for future research. (1) Will the long-term cardiovascular effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II antagonism and renin inhibition be similar or not, and dependent or independent of blood pressure levels? (2) What are the local-regional interactions between vasoconstrictor and vasodilator systems, and does the renin-angiotensin system synchronize these regional hemodynamic regulatory mechanisms? (3) If hypertension is the result of an interaction between genetic and environmental factors, do proteins secreted through constitutive pathways contribute to the genetic abnormality (prorenin, angiotensinogen, ACE) while regulated secretion (renin) and other regulatory mechanisms (angiotensin II receptors) provide biological support for the environmental effects?

Giant renin secretory granules in beige mouse renal afferent arterioles

DEFF Research Database (Denmark)

Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

1997-01-01

The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

Osmotically sensitive renin release from permeabilized juxtaglomerular cells

DEFF Research Database (Denmark)

Jensen, B L; Skøtt, O

1993-01-01

Renin secretion from juxtaglomerular (JG) cells is sensitive to external osmolality in a way that has been suggested to depend either on cellular volume or on effects on secretory granules. To distinguish between these possibilities, a technique for permeabilization of JG cell membranes was devel...

Human renin biosynthesis and secretion in normal and ischemic kidneys

International Nuclear Information System (INIS)

Pratt, R.E.; Carleton, J.E.; Richie, J.P.; Heusser, C.; Dzau, V.J.

1987-01-01

The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing or prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time

Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

Science.gov (United States)

Achard, V; Tassistro, V; Boullu-Ciocca, S; Grino, M

2011-12-01

Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

Annett Juretzko

2017-04-01

Full Text Available Background/Aims: Several studies sought to identify new biomarkers for chronic kidney disease (CKD. As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR. We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. Methods: We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC curves, spearman correlation coefficients and linear regression models were calculated. Results: Urinary angiotensinogen [2,511 (196-31,909 vs. 18.6 (8.3-44.0 pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155 vs. 0.069 (0.045-0.148 pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01 and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01 were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Conclusion: Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease.

Science.gov (United States)

Juretzko, Annett; Steinbach, Antje; Hannemann, Anke; Endlich, Karlhans; Endlich, Nicole; Friedrich, Nele; Lendeckel, Uwe; Stracke, Sylvia; Rettig, Rainer

2017-01-01

Several studies sought to identify new biomarkers for chronic kidney disease (CKD). As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR). We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC) curves, spearman correlation coefficients and linear regression models were calculated. Urinary angiotensinogen [2,511 (196-31,909) vs. 18.6 (8.3-44.0) pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155) vs. 0.069 (0.045-0.148) pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01) and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01) were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may convey additional information beyond that provided by

Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review)

DEFF Research Database (Denmark)

Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

2012-01-01

The question of whether reduced sodium intake is effective as a health prophylaxis initiative is unsolved. The purpose was to estimate the effects of low-sodium vs. high-sodium intake on blood pressure (BP), renin, aldosterone, catecholamines, and lipids....

Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

International Nuclear Information System (INIS)

Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K.

1991-01-01

A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 x 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications

Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system.

Science.gov (United States)

Wang, Lei; Zhu, Qing; Lu, Aihua; Liu, Xiaofen; Zhang, Linlin; Xu, Chuanming; Liu, Xiyang; Li, Haobo; Yang, Tianxin

2017-09-01

Butyrate, a short-chain fatty acid, is the end product of the fermentation of complex carbohydrates by the gut microbiota. Recently, sodium butyrate (NaBu) has been found to play a protective role in a number of chronic diseases. However, it is still unclear whether NaBu has a therapeutic potential in hypertension. The present study was aimed to investigate the role of NaBu in angiotensin II (Ang II)-induced hypertension and to further explore the underlying mechanism. Ang II was infused into uninephrectomized Sprague-Dawley rats with or without intramedullary infusion of NaBu for 14 days. Mean arterial blood pressure was recorded by the telemetry system. Renal tissues, serum samples, and 24-h urine samples were collected to examine renal injury and the regulation of the (pro)renin receptor (PRR) and renin. Intramedullary infusion of NaBu in Sprague-Dawley rats lowered the Ang II-induced mean arterial pressure from 129 ± 6 mmHg to 108 ± 4 mmHg (P renal injury, including urinary albumin, glomerulosclerosis, and renal fibrosis, as well as the expression of inflammatory mediators tumor necrosis factor α, interleukin 6. The renal expression of PRR, angiotensinogen, angiotensin I-converting enzyme and the urinary excretion of soluble PRR, renin, and angiotensinogen were all increased by Ang II infusion but decreased by NaBu treatment. In cultured innermedullary collecting duct cells, NaBu treatment attenuated Ang II-induced expression of PRR and renin. These results demonstrate that NaBu exerts an antihypertensive action, likely by suppressing the PRR-mediated intrarenal renin-angiotensin system.

Radioimmunoassay of renin-angiotensin-aldosterone in patients with adrenal tumors

International Nuclear Information System (INIS)

Slavnov, V.N.; Yakovlev, A.A.; Yugrinov, O.G.; Gandzha, T.I.

1983-01-01

The results are presented of a study of the renin-angiotensin-aldosterone system in 89 patients with aldosteronoma, corticosteroma, pheochromocytoma and hypertension. Radioimmunoassay was used to measure aldosterone concentration and renin activity in the peripheral blood and blood from vena cava inferior, the renal and adrenal veins, the circadian cycle of their content and the responsiveness of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under the influence of lasix intake and the change over from a horizontal into vertical position. Patients with adrenal tumors have shown disorders of renin-angiotensin-aldosterone function. Radioimmunoassay of the renin-angiotensin-aldosterone system promotes early detection of adrenal tumors in the general population of patients with hypertension and can be used for control over therapeutic efficacy

Plasma Renin Activity in Diabetes Mellitus

International Nuclear Information System (INIS)

Pyo, Heui Jung; Park Jung Sik; Kim, Sung Kwon; Choi, Kang Won; Lee, Jung Sang; Lee, Mun Ho

1979-01-01

To evaluate the renin-angiotensin-aldosterone system in diabetes mellitus, basal plasma renin activity (PRA) and its response to intravenous furosemide were determined in 40 diabetic subjects. The diabetics were divided into 4 groups according to the presence of nephropathy and/or hypertension. Uncomplicated diabetics (Group I) were taken as control group and the results of the other groups were compared to this group. In diabetics with nephropathy alone (Group II), and with nephropathy and hypertension (Group III), basal PRA values were 0.63±0.59 ng/ml/hr., and 0.79±0.62 ng/ml/hr., respectively, both significantly lower than control group. (1.53±1.09 ng/ml/hr.). (p<0.05) In both of the above groups, the responses to intravenous furosemide tended to be blunted. On the other hand, in diabetics, with hypertension only (Group IV), the basal and stimulated PRA were not significantly different from control. Above results suggests that nephropathy may be one of the factors which suppress renin activity in diabetes mellitus

Plasma Renin Activity in Diabetes Mellitus

Energy Technology Data Exchange (ETDEWEB)

Pyo, Heui Jung; Sik, Park Jung; Kim, Sung Kwon; Choi, Kang Won; Lee, Jung Sang; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1979-03-15

To evaluate the renin-angiotensin-aldosterone system in diabetes mellitus, basal plasma renin activity (PRA) and its response to intravenous furosemide were determined in 40 diabetic subjects. The diabetics were divided into 4 groups according to the presence of nephropathy and/or hypertension. Uncomplicated diabetics (Group I) were taken as control group and the results of the other groups were compared to this group. In diabetics with nephropathy alone (Group II), and with nephropathy and hypertension (Group III), basal PRA values were 0.63+-0.59 ng/ml/hr., and 0.79+-0.62 ng/ml/hr., respectively, both significantly lower than control group. (1.53+-1.09 ng/ml/hr.). (p<0.05) In both of the above groups, the responses to intravenous furosemide tended to be blunted. On the other hand, in diabetics, with hypertension only (Group IV), the basal and stimulated PRA were not significantly different from control. Above results suggests that nephropathy may be one of the factors which suppress renin activity in diabetes mellitus

Renin-sodium profile and renal prostaglandins in the pathogenesis ...

African Journals Online (AJOL)

the patients having normal-renin hypertension. At basal level the ... finding was in keeping with their low-renin hypertension. ... pathological factor in the development of hypertension in blacks. ... Subjects and methods .... zero sphygmomanometer. ..... Part 11. Biochemistry and endocrine. Hypertension 1990; 15(6): 681-685.

ANGIOTONIN-ACTIVATOR, RENIN- AND ANGIOTONIN-INHIBITOR, AND THE MECHANISM OF ANGIOTONIN TACHYPHYLAXIS IN NORMAL, HYPERTENSIVE, AND NEPHRECTOMIZED ANIMALS.

Science.gov (United States)

Page, I H; Helmer, O M

1940-03-31

1. Angiotonin does not exert its vasoconstrictor effect in the absence of a substance contained in red blood cells and serum which we have called "angiotonin-activator." A fraction has been separated from blood in which angiotonin-activator is concentrated. It contains little or no reninactivator. 2. Repeated intravenous injections of angiotonin into animals causes the pressor response gradually to lessen and finally to disappear (the phenomenon of tachyphylaxis), but much more slowly than when renin is injected. When the response to angiotonin is abolished, renin also fails to act. Large doses of renin reduce and finally abolish the responsiveness to angiotonin. Exhaustion of renin-activator in the blood abolishes the response to renin without abolishing the response to angiotonin. 3. Blood from animals made tachyphylactic by infusion of angiotonin contains greatly reduced amounts of angiotonin-activator. An inhibitor also appears in the blood. 4. Bilateral nephrectomy prolongs and greatly enhances the rise of arterial pressure following injection of angiotonin and renin. The enhancement reaches a maximum in from 24 to 30 hours after operation. Blood from these animals exhibits greatly increased ability to activate angiotonin and renin when tested in isolated perfused organs. Large amounts of angiotonin are required to reduce the amount of activator in their blood. Renin-activator is simultaneously but little affected. 5. Tranfusion of blood from an animal made tachyphylactic to angiotonin into a nephrectomized dog reduces the response of the latter to angiotonin. Angiotonin when added to the blood of the recipient of the transfusion and perfused through a rabbit's ear also exhibits greatly reduced vasoconstrictor action. 6. Transfusion of normal blood in large amounts into nephrectomized or hypertensive dogs reduces the recipient's response to renin. If renintachyphylaxis is established in the donor, transfusion abolishes the response to renin in the recipient

The catalytic mechanism of mouse renin studied with QM/MM calculations.

Science.gov (United States)

Brás, Natércia F; Ramos, Maria J; Fernandes, Pedro A

2012-09-28

Hypertension is a chronic condition that affects nearly 25% of adults worldwide. As the Renin-Angiotensin-Aldosterone System is implicated in the control of blood pressure and body fluid homeostasis, its combined blockage is an attractive therapeutic strategy currently in use for the treatment of several cardiovascular conditions. We have performed QM/MM calculations to study the mouse renin catalytic mechanism in atomistic detail, using the N-terminal His6-Asn14 segment of angiotensinogen as substrate. The enzymatic reaction (hydrolysis of the peptidic bond between residues in the 10th and 11th positions) occurs through a general acid/base mechanism and, surprisingly, it is characterized by three mechanistic steps: it begins with the creation of a first very stable tetrahedral gem-diol intermediate, followed by protonation of the peptidic bond nitrogen, giving rise to a second intermediate. In a final step the peptidic bond is completely cleaved and both gem-diol hydroxyl protons are transferred to the catalytic dyad (Asp32 and Asp215). The final reaction products are two separate peptides with carboxylic acid and amine extremities. The activation energy for the formation of the gem-diol intermediate was calculated as 23.68 kcal mol(-1), whereas for the other steps the values were 15.51 kcal mol(-1) and 14.40 kcal mol(-1), respectively. The rate limiting states were the reactants and the first transition state. The associated barrier (23.68 kcal mol(-1)) is close to the experimental values for the angiotensinogen substrate (19.6 kcal mol(-1)). We have also tested the influence of the density functional on the activation and reaction energies. All eight density functionals tested (B3LYP, B3LYP-D3, X3LYP, M06, B1B95, BMK, mPWB1K and B2PLYP) gave very similar results.

Prediction of renovascualar hypertension by captopril-stimulated renal vein renin ratios

International Nuclear Information System (INIS)

Roubidoux, M.A.; Dunnick, N.R.; Svetkey, L.; Newmann, G.E.; Cohan, R.H.; Kadir, S.; Klotman, P.

1989-01-01

The authors have prospectively studied 114 patients with suspected renovascular hypertension to determine whether captopril-stimulated, selective, renal vein renin ratios could be used to predict renovascular hypertension. As judged by the response to correction of renal artery lesions, 14 patients had renovascular hypertension, and renal vein renin ratios were significant in eight (sensitivity 57%). Overall, the positive predictive value of renal vein renin ratios was 33%, and the negative predictive value was 89%. The authors concluded that, in patients with renal artery stenosis, renal vein renin ratios predict neither the need for conventional arteriography nor potential benefit from the correction of vascular insufficiency

Effects Of The Direct Renin Inhibitor Aliskiren On Oxidative Stress In Isolated Rat Heart

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Plecevic Sasa

2015-09-01

Full Text Available Increased activity of the renin-angiotensin-aldosterone system (RAAS plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g, were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O. Markers of oxidative stress (NO2−, TBARS, H2O2 and O2− were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM. The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2− and hydrogen peroxide (H2O2 levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.

The importance of the renin-angiotensin system in normal cardiovascular homeostasis

Science.gov (United States)

Haber, E.

1975-01-01

Studies were carried out on adult mongrel dogs (20 to 30 kilograms) to investigate the importance of the renin-angiotensin system. Results indicate that the renin-angiotensin system plays a major role in the maintenance of circulatory homeostasis when extracellular fluid volume is depleted. It was also found that angiotensin II concentration, in addition to renal perfusion pressure, is a factor in the regulation of renin release.

Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension.

Science.gov (United States)

Barigou, M; Ah-Kang, F; Orloff, E; Amar, J; Chamontin, B; Bouhanick, B

2015-06-01

To study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening. Fifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51 ± 12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes of seating. Minimal renin value was set at 5 μUI/mL. Referring to ARR cut-off of 23 pg/μUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P<0.001). Current recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23 pg/μUI increased the discriminating power of this test. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Interleukin-1 inhibits renin gene expression in As4.1 cells but not in native juxtaglomerular cells

DEFF Research Database (Denmark)

Jensen, B L; Lehle, U; Müller, Maja

1998-01-01

) cells and in the mouse tumor cell line As4.1, which expresses renin mRNA. Renin mRNA levels and secretion of active renin were not significantly changed by IL-1beta in native JG cells. Activation of adenylyl cyclase by forskolin increased renin secretion and renin mRNA levels three- and fivefold......, respectively. These stimulatory responses to forskolin were not altered by IL-1beta. In contrast to native JG cells, renin mRNA abundance was markedly suppressed by IL-1beta in As4.1 cells, whereas secretion of active renin and the stability of renin mRNA were not changed. In As4.1 cells forskolin did...... not change renin secretion or renin mRNA abundance in the absence or in the presence of IL-1beta. These findings suggest that IL-1beta has no direct influence on renin secretion and renin mRNA abundance at the level of native JG cells....

Plasma Renin Activity in Children with Protein Energy Malnutrition ...

African Journals Online (AJOL)

Plasma renin activity was measured by bio-assay in 100 children with kwashiorkor and in 20 healthy children, and also by radio-immunoassay in another 26 children with kwashiorkor and in another 20 healthy children. Both methods showed that (compared with healthy children) renin activity was significantly increased in ...

Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport

DEFF Research Database (Denmark)

Lorenz, J N; Weihprecht, H; Schnermann, J

1991-01-01

salts to inhibit renin secretion, starting from a stimulated value produced by low-NaCl perfusion. Perfusion with a high-NaCl solution decreased renin secretion from 58.9 to 14.8 nGU/min, which served as a positive control. Addition of choline chloride decreased renin secretion from 42.7 to 16.6 n...

Characterization of renin mRNA expression and enzyme activity in rat and mouse mesangial cells

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Andrade A.Q.

2002-01-01

Full Text Available Renin is an enzyme involved in the stepwise generation of angiotensin II. Juxtaglomerular cells are the main source of plasma renin, but renin activity has been detected in other cell types. In the present study we evaluated the presence of renin mRNA in adult male Wistar rat and mouse (C-57 Black/6 mesangial cells (MC and their ability to process, store and release both the active and inactive forms of the enzyme. Active renin and total renin content obtained after trypsin treatment were estimated by angiotensinogen consumption analyzed by SDS-PAGE electrophoresis and quantified by angiotensin I generation by HPLC. Renin mRNA, detected by RT-PCR, was present in both rat and mouse MC under basal conditions. Active renin was significantly higher (P<0.05 in the cell lysate (43.5 ± 5.7 ng h-1 10(6 cells than in the culture medium (12.5 ± 2.5 ng h-1 10(6 cells. Inactive prorenin content was similar for the intra- and extracellular compartments (9.7 ± 3.1 and 3.9 ± 0.9 ng h-1 10(6 cells. Free active renin was the predominant form found in both cell compartments. These results indicate that MC in culture are able to synthesize and translate renin mRNA probably as inactive prorenin which is mostly processed to active renin inside the cell. MC secrete both forms of the enzyme but at a lower level compared with intracellular content, suggesting that the main role of renin synthesized by MC may be the intracellular generation of angiotensin II.

Vanadate-induced inhibition of renin secretion is unrelated to inhibition Na,K-ATPase activity

Energy Technology Data Exchange (ETDEWEB)

Churchill, P.C.; Rossi, N.F.; Churchill, M.C.; Ellis, V.R. (Wayne State Univ. School of Medicine, Detroit, MI (USA))

1990-01-01

There is evidence that three inhibitors of Na,K-ATPase activity-ouabain, K-free extracellular fluid, and vanadate--inhibit renin secretion by increasing Ca{sup 2+} concentration in juxtaglomerular cells, but in the case of vanadate, it is uncertain whether the increase in Ca{sup 2+} is due to a decrease in Ca{sup 2+} efflux or to an increase in Ca{sup 2+} influx through potential operated Ca channels. In the present experiments, the rat renal cortical slice preparation was used to compare and contrast the effects of ouabain, of K-free fluid, and of vanadate on renin secretion, in the absence and presence of methoxyverapamil, A Ca channel blocker. Basal renin secretory rate averaged 7.7 {plus minus} 0.3 GU/g/60 min, and secretory rate was reduced to nearly zero by 1 mM ouabain, by K-free fluid, by 0.5 mM vanadate, and by K-depolarization. Although 0.5 {mu}M methoxyverapamil completely blocked the inhibitory effect of K-depolarization, it failed to antagonize the inhibitory effects of ouabain, of K-free fluid, and of vanadate.

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial

NARCIS (Netherlands)

de Vries, Laura V.; Dobrowolski, Linn C.; van den Bosch, Jacqueline J. O. N.; Riphagen, Ineke J.; Krediet, C. T. Paul; Bemelman, Frederike J.; Bakker, Stephan J. L.; Navis, Gerjan

2016-01-01

In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade : A Randomized Clinical Trial

NARCIS (Netherlands)

de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown.

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves' disease.

Science.gov (United States)

Mizuguchi, Yuki; Morimoto, Satoshi; Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi; Ichihara, Atsuhiro

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves' Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves' disease than in control subjects (PGraves' disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves' disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves' disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss.

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves’ disease

Science.gov (United States)

Kimura, Shihori; Takano, Noriyoshi; Yamashita, Kaoru; Seki, Yasufumi; Bokuda, Kanako; Yatabe, Midori; Yatabe, Junichi; Watanabe, Daisuke; Ando, Takashi

2018-01-01

Antithyroid drugs are generally selected as the first-line treatment for Graves’ Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves’ disease than in control subjects (Pantithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves’ disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves’ disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss. PMID:29621332

The renin-angiotensin system; development and differentiation of the renal medulla

DEFF Research Database (Denmark)

Madsen, Kirsten; Robdrup Tinning, Anne; Marcussen, Niels

2013-01-01

on mechanisms of postnatal development the renal medulla and putting medullary developmental lesions into perspective with regard to the programming effect. Moreover, the renin-angiotensin system is critically involved in mammalian kidney development and signaling disorders give rise to developmental renal...... disturbances reaching into adulthood. A review of current knowledge of the role of the renin-angiotensin system for renal medullary development will be given. Acta Physiologica © 2013 Scandinavian Physiological Society....... lesions that has been associated with hypertension later in life. A consistent finding in both experimental animal models and in human case reports is atrophy of the renal medulla with developmental lesions to both medullary nephron segments and vascular development with concomitant functional...

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system

DEFF Research Database (Denmark)

Aachmann-Andersen, Niels J.; Christensen, Soren J.; Lisbjerg, Kristian

2018-01-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt...... that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect...... of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system....

Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity.

Science.gov (United States)

Karlberg, B E; Kågedal, B; Tegler, L; Tolagen, K; Bergman, B

1976-03-31

Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (200 mg/day for 2 months), propranolol (320 mg/day for 2 months) and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 +/- 16/7(mean +/- standard deviation) mm Hg supine and 188/118 +/- 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions. Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 +/- 1.2 (range 0.4 to 5.0) ng/ml/hr. There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone. The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and standing positions, irrespective of initial plasma renin activity. All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration. It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone. The combination of the two drugs, which have different modes of action, will effectively reduce blood pressure in hypertension. The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension.

Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

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Fernanda S. Zamo

2010-01-01

Full Text Available BACKGROUND: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1 hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate; 2 left ventricular hypertrophy; and 3 local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. METHODS: Male spontaneously hypertensive rats were randomized into two groups: young (n=13 and adult (n=12. Hemodynamic signals (blood pressure, heart rate, blood pressure variability (BPV and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g, by myocyte diameter (μm and by relative fibrosis area (RFA, %. ACE and ACE2 activities were measured by fluorometry (UF/min, and plasma renin activity (PRA was assessed by a radioimmunoassay (ng/mL/h. Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU. RESULTS: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. CONCLUSIONS: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent

Effects of aqueous extract of Hibiscus sabdariffa on the renin-angiotensin-aldosterone system of Nigerians with mild to moderate essential hypertension: A comparative study with lisinopril.

Science.gov (United States)

Nwachukwu, Daniel Chukwu; Aneke, Eddy Ikemefuna; Obika, Leonard Fidelis; Nwachukwu, Nkiru Zuada

2015-01-01

The present study investigated the effects of aqueous extract of Hibiscus sabdariffa (HS) on the three basic components of renin-angiotensin-aldosterone system: Plasma renin, serum angiotensin-converting enzyme (ACE), and plasma aldosterone (PA) in mild to moderate essential hypertensive Nigerians and compared with that of lisinopril, an ACE inhibitor. A double-blind controlled randomized clinical study was used. Seventy-eight newly diagnosed but untreated mild to moderate hypertensive subjects attending Medical Outpatients Clinic of Enugu State University Teaching Hospital, Enugu were recruited for the study. Those in Group A received placebo (150 mg/kg/day), Group B were given lisinopril (10 mg once daily) while those in Group C received aqueous extract of HS (150 mg/kg/day). After 4 weeks of treatment, the levels of plasma renin, serum ACE, and PA were determined. HS and lisinopril significantly (P < 0.001) reduced PA compared to placebo by 32.06% and 30.01%, respectively. Their effects on serum ACE and plasma renin activity (PRA) were not significant compared to placebo; they reduced ACE by 6.63% and 5.67% but increased plasma PRA by 2.77% and 5.36%, respectively. HS reduced serum ACE and PA in mild to moderate hypertensive Nigerians with equal efficacy as lisinopril. These actions are possibly due to the presence of anthocyanins in the extract.

Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

Energy Technology Data Exchange (ETDEWEB)

Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S. (Medical Center for Postgraduate Education, Warsaw (Poland))

1990-01-01

Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly.

Increased activity of digoxin-like substance in low-renin hypertension in acromegaly

International Nuclear Information System (INIS)

Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S.

1990-01-01

Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly

Human renin 5'-flanking DNA to nucleotide-2750.

Science.gov (United States)

Smith, D L; Jeyapalan, S; Lang, J A; Guo, X H; Sigmund, C D; Morris, B J

1995-01-01

Renin is one of the most important factors in blood pressure and electrolyte regulation in mammals and the renin locus has been implicated in hypertension. To assist studies of promoter control we therefore determined the 5'-flanking sequence of the human gene (REN) to residue -2750 relative to the transcription start site (+1). Sites of homology to consensus sequences for binding of trans-acting factors involved in transcriptional control of other genes were identified, and functionality for two of these (a CRE and Pit-1 site) have so far been demonstrated.

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

Science.gov (United States)

Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

1997-08-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

Effect of breed on plasma endothelin-1 concentration, plasma renin activity, and serum cortisol concentration in healthy dogs

DEFF Research Database (Denmark)

Höglund, K.; Lequarré, A.-S.; Ljungvall, I.

2016-01-01

BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined...... at 5 centers (2-4 breeds/center). METHODS: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including...

Effect of antigravity suit inflation on cardiovascular, PRA, and PVP responses in humans. [Plasma Renin Activity and Plasma VasoPressin

Science.gov (United States)

Kravik, S. E.; Keil, L. C.; Geelen, G.; Wade, C. E.; Barnes, P. R.

1986-01-01

The effects of lower body and abdominal pressure, produced by antigravity suit inflation, on blood pressure, pulse rate, fluid and electrolyte shift, plasma vasopressin and plasma renin activity in humans in upright postures were studied. Five men and two women stood upright for 3 hr with the suit being either inflated or uninflated. In the control tests, the suit was inflated only during the latter part of the trials. Monitoring was carried out with a sphygnomanometer, with sensors for pulse rates, and using a photometer and osmometer to measure blood serum characteristics. The tests confirmed earlier findings that the anti-g suit eliminates increases in plasma renin activity. Also, the headward redistribution of blood obtained in the tests commends the anti-g suit as an alternative to water immersion or bed rest for initial weightlessness studies.

Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure

NARCIS (Netherlands)

D. Westermann (Dirk); A. Riad (Alexander); O. Lettau (Olga); A.J.M. Roks (Anton); K. Sawatis (Konstantinos); P.M. Becher (Peter Moritz); F. Escher (Felicitas); A.H.J. Danser (Jan); H.P. Schultheiss (Heinz-Peter); C. Tschöpe (Carsten)

2008-01-01

textabstractPharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac

The effect of postural changes on plasma renin activity during normal and pathologic pregnancies.

Science.gov (United States)

Brandes, J M; Abramovici, H; Katz, M; Diengott, D; Spindel, A; Kahana, L

1978-11-01

A study of the effect of posture on plasma renin activity (PRA) in the third trimester in 27 gravidas revealed a significantly greater increase in PRA in the supine position, compared to the left lateral. The women were classified into 3 groups: normal pregnancy, preeclampsia, intrauterine fetal death. There was no statistical difference in PRA among the 3 groups. It is assumed that the increase of PRA in the supine position was due mainly to mechanical pressure by the gravid uterus on the great vessels (regardless of whether the fetus was dead or alive) and that effective circulatory volume was thus reduced. However, low PRA in the left lateral position in women with preeclampsia seemed to correlate with more severe disease in these women.

2C.07: INVOLVEMENT OF THE RENIN-ANGIOTENSIN SYSTEM IN A PREMATURE AGING MOUSE MODEL.

Science.gov (United States)

Van Thiel, B S; Ridwan, Y; Garrelds, I M; Vermeij, M; Groningen, M C Clahsen-Van; Danser, A H J; Essers, J; Van Der Pluijm, I

2015-06-01

Changes in the renin-angiotensin system (RAS), known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. Here we characterized the RAS and kidney pathology in mice with genomic instability due to a defective nucleotide excision repair gene (Ercc1d/- mice). These mice display premature features of aging, including vascular dysfunction. Studies were performed in male and female Ercc1d/- mice and their wild type controls (Ercc1+/+) at the age of 12 or 18 weeks before and after treatment with losartan. The renin-activatable near-infrared fluorescent probe ReninSense 680™ was applied in vivo to allow non-invasive imaging of renin activity. Plasma renin concentrations (PRC) were additionally measured ex vivo by quantifying Ang I generation in the presence of excess angiotensinogen. Kidneys were harvested and examined for markers of aging, and albumin was determined in urine. Kidneys of 12-week old Ercc1d/- mice showed signs of aging, including tubular anisokaryosis, cell-senescence and increased apoptosis. This was even more pronounced at the age of 18 weeks. Yet, urinary albumin was normal at 12 weeks. The ReninSense 680™ probe showed increased intrarenal renin activity in Ercc1d/- mice versus Ercc1+/+ mice, both at 12 and 18 weeks of age, while PRC in these mice tended to be lower compared to Ercc1+/+ mice. Renin was higher in male than female mice, both in the kidney and in plasma, and losartan increased kidney and plasma renin in both Ercc1d/- and Ercc1+/+ mice. Rapidly aging Ercc1d/- mice display an activated intrarenal RAS, as evidenced by the increased fluorescence detected with the ReninSense 680™ probe. This increased RAS activity may contribute to the disturbed kidney pathology in these mice. The increased intrarenal activity detected with the ReninSense 680™ probe in male vs. female mice, as well as after losartan treatment, are in full agreement with the literature, and

Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.

Science.gov (United States)

Lotfy, Mahmoud; El-Kenawy, Ayman El-Meghawry; Abdel-Aziz, Mohamed M; El-Kady, Ibrahim; Talaat, Ayman

2010-01-01

Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

NARCIS (Netherlands)

Schroten, Nicolas F.; Damman, Kevin; Hemmelder, Marc H.; Voors, Adriaan A.; Navis, Gerjan; Gaillard, Carlo A. J. M.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Hillege, Hans L.

AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF

Changes in the renin-angiotensin-aldosterone system in response to dietary salt intake in normal and hypertensive pregnancy. A randomized trial

DEFF Research Database (Denmark)

Nielsen, Lise Hald; Ovesen, Per; Hansen, Mie R

2016-01-01

It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or place...... of plasma renin and angiotensin II in response to changes in dietary salt intake compatible with a primary increase in renal sodium reabsorption in hypertensive pregnancies.......It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or placebo...

Renal hemodynamics and renin-angiotensin system activity in humans with multifocal renal artery fibromuscular dysplasia.

Science.gov (United States)

van Twist, Daan J L; Houben, Alphons J H M; de Haan, Michiel W; de Leeuw, Peter W; Kroon, Abraham A

2016-06-01

Fibromuscular dysplasia (FMD) is the second most common cause of renovascular hypertension. Nonetheless, knowledge on the renal microvasculature and renin-angiotensin system (RAS) activity in kidneys with FMD is scarce. Given the fairly good results of revascularization, we hypothesized that the renal microvasculature and RAS are relatively spared in kidneys with FMD. In 58 hypertensive patients with multifocal renal artery FMD (off medication) and 116 matched controls with essential hypertension, we measured renal blood flow (Xenon washout method) per kidney and drew blood samples from the aorta and both renal veins to determine renin secretion and glomerular filtration rate per kidney. We found that renal blood flow and glomerular filtration rate in FMD were comparable to those in controls. Although systemic renin levels were somewhat higher in FMD, renal renin secretion was not elevated. Moreover, in patients with unilateral FMD, no differences between the affected and unaffected kidney were observed with regard to renal blood flow, glomerular filtration rate, or renin secretion. In men, renin levels and renin secretion were higher as compared with women. The renal blood flow response to RAS modulation (by intrarenal infusion of angiotensin II, angiotensin-(1-7), an angiotensin II type 1 receptor blocker, or a nitric oxide synthase blocker) was also comparable between FMD and controls. Renal blood flow, glomerular filtration, and the response to vasoactive substances in kidneys with multifocal FMD are comparable to patients with essential hypertension, suggesting that microvascular function is relatively spared. Renin secretion was not increased and the response to RAS modulation was not affected in kidneys with FMD.

Novel approach of fragment-based lead discovery applied to renin inhibitors.

Science.gov (United States)

Tawada, Michiko; Suzuki, Shinkichi; Imaeda, Yasuhiro; Oki, Hideyuki; Snell, Gyorgy; Behnke, Craig A; Kondo, Mitsuyo; Tarui, Naoki; Tanaka, Toshimasa; Kuroita, Takanobu; Tomimoto, Masaki

2016-11-15

A novel approach was conducted for fragment-based lead discovery and applied to renin inhibitors. The biochemical screening of a fragment library against renin provided the hit fragment which showed a characteristic interaction pattern with the target protein. The hit fragment bound only to the S1, S3, and S3 SP (S3 subpocket) sites without any interactions with the catalytic aspartate residues (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to the hit fragment, we first identified its essential binding sites by utilizing the hit fragment's substructures. Second, we created a new and smaller scaffold, which better occupied the identified essential S3 and S3 SP sites, by utilizing library synthesis with high-throughput chemistry. We then revisited the S1 site and efficiently explored a good building block attaching to the scaffold with library synthesis. In the library syntheses, the binding modes of each pivotal compound were determined and confirmed by X-ray crystallography and the library was strategically designed by structure-based computational approach not only to obtain a more active compound but also to obtain informative Structure Activity Relationship (SAR). As a result, we obtained a lead compound offering synthetic accessibility as well as the improved in vitro ADMET profiles. The fragments and compounds possessing a characteristic interaction pattern provided new structural insights into renin's active site and the potential to create a new generation of renin inhibitors. In addition, we demonstrated our FBDD strategy integrating highly sensitive biochemical assay, X-ray crystallography, and high-throughput synthesis and in silico library design aimed at fragment morphing at the initial stage was effective to elucidate a pocket profile and a promising lead compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of glycaemic control on the effect of direct renin inhibition in the AVOID study

DEFF Research Database (Denmark)

Persson, Frederik; Lewis, Julia B; Lewis, Edmund J

2012-01-01

Hyperglycaemia induces development and progression of microvascular complications in diabetes. A direct link between high glucose levels and intrarenal renin-angiotensin activation has been demonstrated. This post-hoc analysis assessed the influence of baseline glycaemic control on the reduction ...

High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

Science.gov (United States)

Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

2015-11-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

Some Aspects of the Renin-Angiotensin-System in Hemodialysis Patients

Directory of Open Access Journals (Sweden)

Umar Malik

2015-11-01

Full Text Available Understanding of the renin-angiotensin system (RAS has changed remarkably over the past decade. Renin, angiotensin converting enzyme (ACE, angiotensin II (Ang II, and Ang II receptors are the main components of the RAS. Recent studies identified the ACE2/Ang 1-7/Mas receptor axis, which counter-regulates the classical RAS. Many studies have examined the effects of the RAS on the progression of cardiovascular disease and chronic kidney disease (CKD. In addition, many studies have documented increased levels of ACE in hemodialysis (HD patients, raising concerns about the negative effects of RAS activation on the progression of renal disease. Elevated ACE increases the level of Ang II, leading to vasoconstriction and cell proliferation. Ang II stimulation of the sympathetic system leads to renal and cardiovascular complications that are secondary to uncontrolled hypertension. This review provides an overview of the RAS, evaluates new research on the role of ACE2 in dialysis, and reviews the evidence for potentially better treatments for patients undergoing HD. Further understanding of the role of ACE and ACE2 in HD patients may aid the development of targeted therapies that slow the progression of CKD and cardiovascular disease.

MboI RFLP at the human renin (ren) gene locus

Energy Technology Data Exchange (ETDEWEB)

Masharani, U; Frossard, P M

1988-03-25

1.5kb full length human renin cDNA was isolated from a human kidney cDNA library and subcloned into pUC9. MboI (GATC) detects a single two allele polymorphism with fragments at either 1.4kb or 1.0kb. The frequency was studied in 80 unrelated North American. The human renin gene was assigned to chromosome 1 by southern blot analysis of DNA from human-rodent somatic cell hybrids. Codominant segregation was observed in 1 family (7 individuals).

The evolution of renin-angiotensin blockade: angiotensin-converting enzyme inhibitors as the starting point.

Science.gov (United States)

Sica, Domenic A

2010-04-01

The renin-angiotensin system has been a target in the treatment of hypertension for close to three decades. Several medication classes that block specific aspects of this system have emerged as useful therapies, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and, most recently, direct renin inhibitors. There has been a natural history to the development of each of these three drug classes, starting with their use as antihypertensive agents; thereafter, in each case they have been employed as end-organ protective agents. To date, there has been scant evidence to favor angiotensin receptor blockers or direct renin inhibitors over angiotensin-converting enzyme inhibitors in treating hypertension or in affording end-organ protection; thus, angiotensin-converting enzyme inhibitors remain the standard of care when renin-angiotensin system blockade is warranted.

Characterization of the macula densa stimulus for renin secretion

DEFF Research Database (Denmark)

Lorenz, J N; Weihprecht, H; Schnermann, J

1990-01-01

These studies utilize the isolated perfused rabbit juxtaglomerular apparatus (JGA) to study the macula densa signal for renin secretion in the absence of the confounding influences of intravascular pressure and renal nerve activity. In the first experimental series, JGAs were perfused alternately...... and decreases in macula densa NaCl concentration, and these changes are rapid and largely reversible, 2) the full renin response occurs within the concentration range normally occurring at the macula densa, i.e., below 80 mM Na+ and 61 mM Cl-, and 3) RSR responds with a larger change to alterations in Na...

Effect of hypovolemia, infusion, and oral rehydration on plasma electrolytes, ADH, renin activity, and +G/z/ tolerance

Science.gov (United States)

Greenleaf, J. E.; Brock, P. J.; Haines, R. F.; Rositano, S. A.; Montgomery, L. D.; Keil, L. C.

1977-01-01

Effects on plasma volume, electrolyte shifts, and +G(z) tolerance induced by: (1) blood withdrawal; (2) blood infusion; and (3) oral fluid intake, were determined at 0.5 G/min in centrifugation tests of six ambulatory male patients, aged 21 to 27 yrs. Hypovolemia induced by withdrawal of 400 ml blood, blood infusion followed by repeated centrifugation, effects of consuming an isotonic drink (0.9% NaCl) to achieve oral rehydration, and donning of red adaptation goggles were studied for effects on acceleration tolerance, pre-acceleration and post-acceleration plasma renin activity (PRA) and plasma vasopressin levels. No significant changes in post-acceleration PRA compared to pre-acceleration PRA were found, and administration of oral rehydration is found as effective as blood replacement in counteracting hypovolemic effects.

Contribution of the basolateral isoform of the Na-K-2Cl- cotransporter (NKCC1/BSC2) to renin secretion

DEFF Research Database (Denmark)

Castrop, Hayo; Lorenz, John N; Hansen, Pernille B

2005-01-01

Acute administration of loop diuretics like furosemide leads to a stimulation of renin secretion, an effect thought to result from inhibition of Na-K-2Cl cotransporter (NKCC2)-mediated salt transport at the luminal surface of the macula densa (MD). However, loop diuretics also inhibit NKCC1......, the second isoform of the Na-K-2Cl cotransporter, with similar potency. In the present study, we examined the influence of furosemide on renin secretion in NKCC1-deficient mice to distinguish between effects of the loop diuretic involving NKCC2 and, by implication, the MD pathway, and effects that might...

Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

Directory of Open Access Journals (Sweden)

Zhen-Ye Zhang

2017-09-01

Full Text Available Large-conductance calcium-activated potassium channels (BK channels belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone system has profound influences on the expression and bioactivity of BK channels. In this review, we focus on the molecular mechanisms underlying the regulation of BK channels mediated by the renin-angiotensin-aldosterone system and its potential as a target for clinical drugs.

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

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V Raghunathan

2017-01-01

Full Text Available Hypertension is common in hemolytic uremic syndrome (HUS and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

Effect of all-trans retinoic acid treatment on prohibitin and renin-angiotensin-aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury.

Science.gov (United States)

Zhou, Tian-Biao; Ou, Chao; Rong, Liang; Drummen, Gregor P C

2014-09-01

All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA (PHB1: r = -0.792, -0.834, -0.805, -0.795, -0.778, -0.798, -0.751, -0.682; PHB2: r = -0.872, -0.799, -0.838, -0.773, -0.769, -0.841, -0.794, -0.826; each p system under hypoxia/reoxygenation conditions. © The Author(s) 2014.

Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

DEFF Research Database (Denmark)

Jensen, B L; Skøtt, O

1996-01-01

or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate....... Norepinephrine (5 x 10(-7)-1 x 10(-6) M) and angiotensin II (1 x 10(-8)-10(-6) M) evoked reversible and dose-dependent contractions of microperfused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the basal diameter of the arterioles but strongly inhibited the response to angiotensin II and attenuated...

Iminopyrimidinones: A novel pharmacophore for the development of orally active renin inhibitors

Energy Technology Data Exchange (ETDEWEB)

McKittrick, Brian A.; Caldwell, John P.; Bara, Thomas; Boykow, George; Chintala, Madhu; Clader, John; Czarniecki, Michael; Courneya, Brandy; Duffy, Ruth; Fleming, Linda; Giessert, Rachel; Greenlee, William J.; Heap, Charles; Hong, Liwu; Huang, Ying; Iserloh, Ulrich; Josien, Hubert; Khan, Tanweer; Korfmacher, Walter; Liang, Xian; Mazzola, Robert; Mitra, Soumya; Moore, Kristina; Orth, Peter; Rajagopalan, Murali; Roy, Sudipta; Sakwa, Samuel; Strickland, Corey; Vaccaro, Henry; Voigt, Johannes; Wang, Hongwu; Wong, Jesse; Zhang, Rumin; Zych, Andrew (Merck); (Albany MR)

2015-04-01

The development of renin inhibitors with favorable oral pharmacokinetic profiles has been a longstanding challenge for the pharmaceutical industry. As part of our work to identify inhibitors of BACE1, we have previously developed iminopyrimidinones as a novel pharmacophore for aspartyl protease inhibition. In this letter we describe how we modified substitution around this pharmacophore to develop a potent, selective and orally active renin inhibitor.

Radioimmunologic analysis of the state of the renin-angiotensin-aldosterone-system in arterial hypertension

International Nuclear Information System (INIS)

Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G.

1985-01-01

In 110 patients suffering from various forms of arterial hypertension (hypertension, aldosteronoma, phaeochromocytoma, corticosteroma) the parameters of the system renin-angiotensin-aldosterone were measured. Basal values of aldosterone, renin activity in blood as well as their concentration in blood taken from the vena cava inferior, renal and adrenal veins during selective renography were determined. The 24-hours rhythm of the hormones in the blood, the reaction of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under acute Lasix (furosemide) stress was evaluated. It was found, that the system renin-angiotensin-aldosterone is disturbed in all patients with arterial hypertension. This is indicated by changes of aldosterone concentration, renin activity in peripheral blood and in the blood from the vena cava inferior, renal and adrenal veins, the 24-hours rhythm of their concentrations in serum and the reaction to acute Lasix stress. The radioimmunoassays of quantitative parameters of the renin-angiotensin-aldosterone system are decisive for the differential diagnosis of hypertension and adrenal gland tumors connected with a hypertension syndrome. They facilitate a rational choice of the hypertension therapy and the daily distribution of the medicaments for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medicaments and surgery. (author)

Studies on renin stimulation in normal controls and in patients with essential hypertension

International Nuclear Information System (INIS)

Koh, C.S.; Choe, K.W.; Lee, H.K.; Lee, J.S.

1978-01-01

To find out a convenient and reliable method of detecting low renin status, we employed intravenous furosemine injection as a stimulatory maneuver. The results thus obtained were compared with those from the postural stimuli and basal plasma renin activity (PRA) in relation to sodium excretion. Intravenous furosemide test was performed in 66 control subjects and 44 patients with essential hypertension. The results were as follow; 1) Mean PRA in control subjects rose from 2.5+-1.95 ng/ml/hr (basal) to 4.5+-2.51, 5.2+-2.49 and 4.2+-2.44 ng/ml/hr at 1, 2 and 3hrs after IV injection. One-hour response is more convenient in clinical practice. 2) Postural stimuli by assuming an upright posture for 3hrs gave rise to considerable increase in PRA (4.0+-2.92 from 2.4+-1.85), but we found it less convenient than stimulation with furosemide. 3) The increase in PRA was much less marked in patients with essential hypertension as a whole (2.9+-2.75). Hyporesponsiveness to furosemide stimuli was found in 34.1%. Of these hyporesponders, a third had a normal basal PRA, indicating the need for this kind stimulatory procedure. 4) Younger age group showed greater renin responsiveness than older age group after furosemide stimuli. Likewise mean age of low renin patients (52.9+-5.38 years old) was significantly higher than that of high and normal renin patients (44.1+-13.78 years old). (author)

Studies on Renin Stimulation in Normal Controls and in Patients with Essential Hypertension

Energy Technology Data Exchange (ETDEWEB)

Koh, Chang Soon; Choe, Kang Won; Lee, Hong Kyu; Lee, Jung Sang [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1978-03-15

To find out a convenient and reliable method of detecting low renin status, we employed intravenous furosemide injection as a stimulatory maneuver. The results thus obtained were compared with those from the postural stimuli and basal plasma renin activity (PRA) in relation to sodium excretion. Intravenous furosemide test was performed in 66 control subjects and 44 patients with essential hypertension. The results were as follow; 1) Mean PRA in control subjects rose from 2.5+-1.95 ng/ml/hr (basal) to 4.5+-2.51, 5.2+-2.49 and 4.2+-2.44 ng/ml/hr at 1, 2 and 3 hrs after IV injection. One-hour response is more convenient in clinical practice. 2) Postural stimuli by assuming an upright posture for 3 hrs gave rise to considerable increase in PRA (4.0+-2.92 from 2.4+-1.85), but we found it less convenient than stimulation with furosemide. 3) The increase in PRA was much less marked in patients with essential hypertension as a whole (2.9+-2.75). Hyporesponsiveness to furosemide stimuli was found in 34.1%. Of these hyporesponders, a third had a normal basal PRA, indicating the need for this kind stimulatory procedure. 4) Younger age group showed greater renin responsiveness than older age group after furosemide stimuli. Likewise mean age of low renin patients (52.9+-5.38 years old) was significantly higher than that of high and normal renin patients (44.1+-13.78 years old).

Plasma renin activity, aldosterone and catecholamine levels when swimming and running.

Science.gov (United States)

Guezennec, C Y; Defer, G; Cazorla, G; Sabathier, C; Lhoste, F

1986-01-01

The purpose of this study was to determine the response of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and catecholamines to two graded exercises differing by posture. Seven male subjects (19-25 years) performed successively a running rest on a treadmill and a swimming test in a 50-m swimming pool. Each exercise was increased in severity in 5-min steps with intervals of 1 min. Oxygen consumption, heart rate and blood lactate, measured every 5 min, showed a similar progression in energy expenditure until exhaustion, but there was a shorter time to exhaustion in the last step of the running test. PRA, PAC and catecholamines were increased after both types of exercise. The PRA increase was higher after the running test (20.9 ng AngI X ml-1 X h-1) than after swimming (8.66 ng AngI X ml-1 X h-1). The PAC increase was slightly greater after running (123 pg X ml-1) than swimming (102 pg X ml-1), buth the difference was not significant. Plasma catecholamine was higher after the swimming test. These results suggest that the volume shift induced by the supine position and water pressure during swimming decreased the PRA response. The association after swimming compared to running of a decreased PRA and an enhanced catecholamine response rule out a strict dependence of renin release under the effect of plasma catecholamines and is evidence of the major role of neural pathways for renin secretion during physical exercise.

Effect of PTA on blood pressure, renal plasma flow and renal venous renin activity in renovascular hypertension

International Nuclear Information System (INIS)

Arlart, I.P.; Dewitz, H. von; Rosenthal, J.

1983-01-01

Percutaneous transluminal angioplasty (PTA) is more and more accepted for interventional management of renal artery stenosis in hypertensive patients. This study was carried out to assess the behaviour of arterial blood-pressure, renal plasma flow and renal venous rening activity in renovascular hypertension following catheter dilatation. Using the data the possibility is calculated to predict the effect of PTA on blood pressure preinterventionally. The results demonstrate that a successful employment of PTA depends on a normal contralateral renal plasma flow and a normalization of plasma flow of the poststenotic kidney. Determination of plasma renin activity is only of restricted value. (orig.)

Pharmacokinetic/Pharmacodynamic Modeling of Renin-Angiotensin Aldosterone Biomarkers Following Angiotensin-Converting Enzyme (ACE) Inhibition Therapy with Benazepril in Dogs.

Science.gov (United States)

Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Soubret, Antoine; Giraudel, Jérôme M; Danhof, Meindert

2015-06-01

The objective of this research was to provide a comprehensive description of the effect of benazepril on the dynamics of the renin-angiotensin aldosterone system (RAAS) in dogs. Blood specimens for renin activity (RA), angiotensin II (AII), and aldosterone (ALD) quantitation in plasma were drawn from 12 healthy adult beagle dogs randomly allocated to 2 treatment groups: (i) benazepril 5 mg PO, q24 h (n: 6) and (ii) placebo (n: 6), in a cross-over design. A mechanism-based pharmacokinetic/pharmacodynamic model, which includes the periodic nature of RA, AII, and ALD during placebo treatment and the subsequent changes in dynamics following repeated dosing with benazepril, was developed. The disposition kinetics of benazepril active metabolite, benazeprilat, was characterized using a saturable binding model to the angiotensin converting enzyme. The modulatory effect of benazeprilat on the RAAS was described using a combination of immediate response models. Our data show that benazepril noticeably influences the dynamics of the renin cascade, resulting in a substantial decrease in AII and ALD, while increasing RA throughout the observation span. The model provides a quantitative framework for better understanding the effect of ACE inhibition on the dynamics of the systemic RAAS in dogs.

Studies on Renin Stimulation in Normal Controls and in Patients with Essential Hypertension

International Nuclear Information System (INIS)

Koh, Chang Soon; Choe, Kang Won; Lee, Hong Kyu; Lee, Jung Sang

1978-01-01

To find out a convenient and reliable method of detecting low renin status, we employed intravenous furosemide injection as a stimulatory maneuver. The results thus obtained were compared with those from the postural stimuli and basal plasma renin activity (PRA) in relation to sodium excretion. Intravenous furosemide test was performed in 66 control subjects and 44 patients with essential hypertension. The results were as follow; 1) Mean PRA in control subjects rose from 2.5±1.95 ng/ml/hr (basal) to 4.5±2.51, 5.2±2.49 and 4.2±2.44 ng/ml/hr at 1, 2 and 3 hrs after IV injection. One-hour response is more convenient in clinical practice. 2) Postural stimuli by assuming an upright posture for 3 hrs gave rise to considerable increase in PRA (4.0±2.92 from 2.4±1.85), but we found it less convenient than stimulation with furosemide. 3) The increase in PRA was much less marked in patients with essential hypertension as a whole (2.9±2.75). Hyporesponsiveness to furosemide stimuli was found in 34.1%. Of these hyporesponders, a third had a normal basal PRA, indicating the need for this kind stimulatory procedure. 4) Younger age group showed greater renin responsiveness than older age group after furosemide stimuli. Likewise mean age of low renin patients (52.9±5.38 years old) was significantly higher than that of high and normal renin patients (44.1±13.78 years old).

Atrial distension, haemodilution, and acute control of renin release during water immersion in humans

DEFF Research Database (Denmark)

Gabrielsen, A; Pump, B; Bie, P

2002-01-01

immersion. During WI, central venous pressure (CVP) and left atrial diameter (LAD) increased (P ... is not the single pivotal stimulus for the acute suppression of renin release in response to intravascular volume expansion by water immersion in humans. Haemodilution constitutes a significant and conceivably the principal stimulus for the acute immersion-induced suppression of renin-angiotensin system activity....

[Renin-angiotensin-aldosterone system activity during head-up tilt testing in patients with vasovagal syncope].

Science.gov (United States)

Gajek, Jacek; Zyśko, Dorota; Mazurek, Walentyna

2005-08-01

The stimulation of renin-angiotensin-aldosterone (RAA) system during tilt table test is caused by sympathetic nervous system activation by orthostatic stress and a serotonin release as well. In healthy individuals increase of plasma renin activity during test with maximal values on the peak of the test was described. The aim of the study was to assess the activation of RAAS in patients with neurally mediated syncope during the tilt table test by means of plasma renin activity and serum aldosterone levels. The study was carried out in 31 patients aged 39.4 +/- 15.0 years (18 women and 13 men) with neurally mediated syncope during tilt test. Plasma renin activity was assessed in the baseline conditions, immediately after the test and 10 minutes after the test using radioenzymatic assay. Aldosterone concentrations were measured radioimmunologically, twice: after 30 minutes supine rest and after the syncope. Plasma renin activity during supine rest was 2.2 +/- 2.4 ng/ml/h, rose after the syncope 2.5-fold to 5.2 +/- 4.5 ng/ml/h (p < 0.001 comparing to baseline) stayed on similar level approximately for the next 10 minutes--4.9 +/- 5.5 ng/ml/h (p = n.s.). In 11 patients (35%) 10 minutes after the test even further increase of PRA was observed. Serum aldosterone level increased significantly immediately after tilt test (90.0 +/- 72.9 vs 178.8 +/- 150.1 pg/ml, p < 0.01). Authors showed, that in patients with NMS plasma renin activity increases and this increase lasts for 10 minutes after the syncope and the concentration of aldosterone increases immediately after tilt test.

Improved interpretation of renal-vein-renin-ratio by simultaneous determination of renal 131I-hippuric-acid-clearance-ratio in patients with renovascular hypertension

International Nuclear Information System (INIS)

Helber, A.; Boenner, G.; Hummerich, W.; Wambach, G.; Meurer, K.A.; Dvorak, K.; Lent, V.; Zehle, A.; Kaufmann, W.; Koeln Univ.; Staedtisches Krankenhaus Koeln-Merheim; Staedtisches Krankenhaus Koeln-Merheim; Koeln Univ.

1979-01-01

In patients with unilateral vascular kidney disease and hypertension, ratio of renal-vein-renin was compared with 131 I-Hippuric-acid clearance and change in blood pressure during Saralasininfusion. The ratio of renal-vein-renin was positively correlated with the ratio in renal plasma flow between the kidneys in all patients studied. The ratio of renins therefore is a result of two factors: The difference in renin secretion and the difference in blood flow in the two kidneys. In patients with angiotensin independent hypertension renin-ratios up to 2.0 were found without relevance to elevated blood pressure. When the difference in renal blood flow between both kidneys was small, even a slight difference in renal vein renin indicated hypertension related to increased renin secretion. (orig./AJ) [de

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system.

Science.gov (United States)

Aachmann-Andersen, Niels J; Christensen, Soren J; Lisbjerg, Kristian; Oturai, Peter; Johansson, Pär I; Holstein-Rathlou, Niels-Henrik; Olsen, Niels V

2018-03-01

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high-dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin-angiotensin-aldosterone system from changes in renal hemodynamics. This may serve as a negative feed-back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin-angiotensin-aldosterone system. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells

DEFF Research Database (Denmark)

Desch, Michael; Schreiber, Andrea; Schweda, Frank

2010-01-01

We recently found that endogenous (free fatty acids) and pharmacological (thiazolidinediones) agonists of nuclear receptor Peroxisome proliferator-activated receptor (PPAR)gamma stimulate renin transcription. In addition, the renin gene was identified as a direct target of PPARgamma. The mouse re...

Direct demonstration of macula densa-mediated renin secretion

DEFF Research Database (Denmark)

Skøtt, O; Briggs, J P

1987-01-01

An in vitro method has been used to examine whether secretion of renin from the juxtaglomerular apparatus is affected by changes in the sodium chloride concentration of the tubular fluid at the macula densa. Single juxtaglomerular apparatuses were microdissected from rabbits and the tubule segmen...

Plasma renin activity in patients with ischaemic heart disease

International Nuclear Information System (INIS)

Urbanek, J.; Hofman, O.; Reisenauer, R.; Slaby, A.

1977-01-01

Plasma renin activity (PRA) stimulated by upright posture was measured in 300 men aged 45-64 years using a radioimmunoassay of angiotensin-I. The examined subjects were normotensive or patients with benign essential hypertension and were divided into 6 groups according to the absence of manifest atherosclerosis, the presence of definite angina pectoris or a history of myocardial infarction. Each group contained 50 unselected subjects, with a comparable mean age. Significant differences in mean PRA were found between corresponding groups of hypertensives and normotensives, the values in hypertensives being lower. The percentage of low renin values was higher in hypertensives with ischaemic heart disease than in other groups. It is suggested that this finding might be explained by functional disturbances in the kidneys in hypertensives with ischaemic heart disease. (orig.) [de

Plasma renin activity in patients with ischaemic heart disease

Energy Technology Data Exchange (ETDEWEB)

Urbanek, J; Hofman, O; Reisenauer, R; Slaby, A [Karlova Universita, Prague (Czechoslovakia). Inst. of Biophysics and Nuclear Medicine; Karlova Universita, Prague (Czechoslovakia). IV. Dept. of Internal Medicine; Vyzkumny Ustav Endokrinologicky, Prague [Czechoslovakia

1977-04-01

Plasma renin activity (PRA) stimulated by upright posture was measured in 300 men aged 45 to 64 years using a radioimmunoassay of angiotensin-I. The examined subjects were normotensive or patients with benign essential hypertension and were divided into 6 groups according to the absence of manifest atherosclerosis, the presence of definite angina pectoris or a history of myocardial infarction. Each group contained 50 unselected subjects, with a comparable mean age. Significant differences in mean PRA were found between corresponding groups of hypertensives and normotensives, the values in hypertensives being lower. The percentage of low renin values was higher in hypertensives with ischaemic heart disease than in other groups. It is suggested that this finding might be explained by functional disturbances in the kidneys in hypertensives with ischaemic heart disease.

Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

Science.gov (United States)

Giles, Thomas D; Bakris, George; Oparil, Suzanne; Weber, Michael A; Li, Huiling; Mallick, Madhuja; Bharucha, David B; Chen, ChunLin; Ferguson, William G

2015-11-01

After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes

DEFF Research Database (Denmark)

Pedersen-Bjergaard, U.; Dhamrait, S.S.; Sethi, A.A.

2008-01-01

BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system...... are similarly associated. METHODS: Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma...... associate with high risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of renin-angiotensin system blocking drugs in patients with recurrent severe hypoglycemia merits further investigation Udgivelsesdato: 2008/3...

The role of renin angiotensin system intervention in stage B heart failure.

LENUS (Irish Health Repository)

Collier, Patrick

2012-04-01

This article outlines the link between the renin angiotensin aldosterone system (RAAS) and various forms of cardiomyopathy, and also reviews the understanding of the effectiveness of RAAS intervention in this phase of ventricular dysfunction. The authors focus their discussion predominantly on patients who have had previous myocardial infarction or those who have left ventricular hypertrophy and also briefly discuss the role of RAAS activation and intervention in patients with alcoholic cardiomyopathy.

Negative captopril renography on patients with renin mediated hypertension due to page kidney and reninoma

International Nuclear Information System (INIS)

Yung, B.C.K.; Wong, K.W.; Fan, W.C.; Chan, J.C.S.; Lo, S.S.S.

1999-01-01

Through a mechanism similar to renal artery stenosis, patients with reninoma and page kidney also suffered from renin mediated hypertension. Captopril renograms performed on our patients with the latter two conditions, however, did not yield diagnostic findings. Therefore, equivocal or negative captopril renography cannot serve to rule out conditions with elevated renin other than renal artery stenosis

Associations of aldosterone and renin concentrations with inflammation-the Study of Health in Pomerania and the German Conn's Registry.

Science.gov (United States)

Grotevendt, A; Wallaschofski, H; Reincke, M; Adolf, C; Quinkler, M; Nauck, M; Hoffmann, W; Rettig, R; Hannemann, A

2017-08-01

Chronic inflammation is an age-independent and body mass index-independent contributor to the development of multi-morbidity. Alterations of the renin-angiotensin-aldosterone system are observed within the context of proinflammatory states. We assessed circulating aldosterone, renin, and inflammatory biomarker concentrations in healthy, normotensive subjects and patients with primary aldosteronism. We included 1177 normotensive individuals from the population-based Study of Health in Pomerania (first follow-up, Study of Health in Pomerania-1) and 103 primary aldosteronism patients from the German Conn's Registry. A 1:1 matching for sex, age, body mass index, smoking status, diabetes mellitus, and the estimated glomerular filtration rate was performed to determine whether primary aldosteronism patients exhibit higher inflammatory biomarker concentrations than normotensive controls. The associations of plasma aldosterone concentration or plasma renin concentration with circulating fibrinogen concentrations, white blood cell count, and high sensitive C-reactive protein concentrations in the normotensive sample were determined with multivariable linear and logistic regression analyses. 1:1 matched primary aldosteronism patients demonstrated significantly (p < 0.01) higher plasma aldosterone concentration (198 vs. 47 ng/l), lower plasma renin concentration (3.1 vs. 7.7 ng/l) and higher high sensitive C-reactive protein concentrations (1.5 vs. 1.0 mg/l) than normotensive controls. Within the normotensive cohort, plasma renin concentration but not plasma aldosterone concentration was positively associated with fibrinogen concentrations and white blood cell count. Further, a J-shaped association between plasma renin concentration and high sensitive C-reactive protein concentrations was detected. High plasma aldosterone concentration in a primary aldosteronism cohort and high plasma renin concentration in normotensive subjects are associated with increased

Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus : effects of RAAS stimulation

NARCIS (Netherlands)

Luik, PT; Kerstens, MN; Hoogenberg, K; Navis, GJ; Dullaart, RPF

Background Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity

Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man

Science.gov (United States)

Convertino, V. A.; Keil, L. C.; Bernauer, E. M.; Greenleaf, J. E.

1981-01-01

The influence of work intensity on plasma volume, osmolality, vasopressin and renin activity and the interrelationships between these responses are investigated. Plasma volume, renin activity and osmotic, sodium and arginine vasopressin concentrations were measured in venous blood samples taken from 15 healthy male subjects before and after six minutes of bicycle ergometer exercise at 100, 175 and 225 W. Plasma volume is found to decrease significantly with increasing work intensity, while increases in Na(+) concentration, osmolality and vasopressin are only observed to be significant when the work intensity exceeds 40% maximal aerobic capacity and plasma resin activity increased linearly at all work levels. In addition, significant correlations are observed between plasma volume and osmolality and sodium changes, and between vasopressin and osmolality and sodium content changes. Data thus support the hypotheses that (1) vasopressin may be the primary controlling endocrine for fluid and electrolyte levels following exercise; (2) an exercise intensity greater than 40% maximal aerobic capacity is required to stimulate vasopressin release through changes in plasma osmolality; and (3) the stimulation of the renin-angiotensin system is a more general stress response.

Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

Science.gov (United States)

Verdonk, Koen; Saleh, Langeza; Lankhorst, Stephanie; Smilde, J E Ilse; van Ingen, Manon M; Garrelds, Ingrid M; Friesema, Edith C H; Russcher, Henk; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

2015-06-01

Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness

Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

Science.gov (United States)

Anderson, W P; Johnston, C I; Korner, P I

1979-01-01

1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance. PMID:219182

The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

DEFF Research Database (Denmark)

Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen

2012-01-01

A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype...

Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik

2009-01-01

Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the n......Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment...... both subjects at low and at high risk within a one-year period were identified. Preliminary data suggest that this is explained by impaired capability of subjects with high renin-angiotensin system activity to maintain cognitive function during hypoglycaemia. The clinical implications of this finding...... which, however, must await additional independent confirmation, include prediction and possibly some prevention of severe hypoglycaemia. An evaluation of renin-angiotensin system activity may - together with assessment of other risk factors - contribute to rational individualized setting of glycaemic...

The renin-angiotensin system and its blockers

Directory of Open Access Journals (Sweden)

Igić Rajko

2014-01-01

Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

A case of low renin hyperaldosteronism considered to be aldosterone-producing adrenocortical adenoma by CT image of adrenal gland

International Nuclear Information System (INIS)

Hayashi, Kozo; Tsuchihashi, Yoshihiro; Ito, Kazuro; Ozono, Noboru

1983-01-01

A case was reported in which hypertension, hypopotassemia, low plasma renin activity and hyperaldosteronemia were observed. Imaging suggested adrenocortical adenoma, leading to the diagnosis of low renin hyperaldosteronism. (Chiba, N.)

Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice

NARCIS (Netherlands)

Rosendahl, Alva; Niemann, Gianina; Lange, Sascha; Ahadzadeh, Erfan; Krebs, Christian; Contrepas, Aurelie; van Goor, Harry; Wiech, Thorsten; Bader, Michael; Schwake, Michael; Peters, Judith; Stahl, Rolf; Nguyen, Genevieve; Wenzel, Ulrich

Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is

High maternal sodium intake alters sex-specific renal renin-angiotensin system components in newborn Wistar offspring.

Science.gov (United States)

Maia, D R R; Lopes, K L; Heimann, J C; Furukawa, L N S

2016-01-28

This study aimed to evaluate the systemic and renal renin-angiotensin-aldosterone system (RAAS) at birth in male and female offspring and in mothers fed a high sodium diet (HSD) before and during gestation. Female Wistar rats were fed a HSD (8.0% NaCl) or a normal sodium diet (1.3% NaCl) from 8 weeks of age until delivery of their first litter. Maternal body weight, tail blood pressure, and food and water intake were evaluated. The litter sizes were assessed, and the body and kidney weights of the offspring were measured. Both mothers and offspring were euthanized immediately following the birth of the pups to evaluate plasma renin activity (PRA), renal renin content (RRC), renal angiotensin-converting enzyme (ACE) activity, renal angiotensin (Ang) II content, serum aldosterone (ALDO) levels, and renal cortical and medullary renin messenger RNA expression. In mothers in the HSD group, water intake and kidney mass were higher, whereas renal ACE activity, Ang II, PRA, ALDO and RRC were decreased. In the offspring of HSD-fed dams, the body and kidney mass were lower in both genders, renal ACE activity was lower in females and renal Ang II was lower in males. PRA, RRC, renin gene expression and ALDO levels did not differ between the groups of offspring. The data presented herein showed that a maternal HSD during pregnancy induces low birth weight and a sex-specific response in the RAAS in offspring.

Fundamental and clinical study of direct immunoradiometric assay in human renin concentration

International Nuclear Information System (INIS)

Kurimoto, Fumihiko; Horiuchi, Junko; Sakurai, Hyoichiro; Suzuki, Hiromichi; Takita, Takashi; Saruta, Takao.

1988-01-01

'Renin RIA Pasteur' kit for directly measuring renin concentration in human plasma (PRC) was fundamentally and clinically evaluated. A standard curve for PRC was linear in the range of 10 - 640 pg/ml. Reproducibility, recovery, and stability were satisfactory. There was a significantly positive correlation between direct PRC and conventional plasma renin activity (PRA) and indirect PRC. PRC was directly measured in 119 healthy volunteers and 15 patients with primary aldosteronism (4), Cushing's syndrome (6), or non-functioning tumor (5). The basal PRC was 32.4 +- 18.8 pg/ml for men and 37.9 +- 22.6 pg/ml for women. PRC for primary aldosteronism was below detectable levels, and remained unchanged even after the administratin of ACTH. In the case of Cushing's syndrome, mean PRC and PRA were 19 pg/ml and 1.2 ng/ml/hr, and did not respond to ACTH. Although the administration of ATCH was significantly associated with a decreased PRC, there was only tendency toward the decreased PRA in the case of non-functioning tumors. The results indicate the usefulness of the present kit in terms of its ability to directly measure PRC without any complicated procedures. (Namekawa, K.)

A Study on Renin-Angiotensin System and Total Exchangeable Sodium in Hypertension

International Nuclear Information System (INIS)

Choe, Kang Won; Park, Jung Sik; Lee, Jung Sang; Koh, Chang Soon

1976-01-01

The etiologic role of renin-angiotensin system and sodium-volume status in the pathophysiology of various forms of hypertension was investigated. Plasma renin activity (PRA) was measured by radioimmunoassay, while sodium-volume status was evaluated by the determination of total exchangeable sodium(NaE) using isotope dilution method. The subjects consisted of 25 controls, 24 patients with essential hypertension, 22 patients with chronic renal failure (13 with hypertension, 9 without hypertension) and 14 patients with malignant hypertension. The results were as follows: 1) An inverse correlation between NaE and PRA was noted in control subjects (r=-0.598, p 0.1) 3) Absolute value of PRA was not deviated significantly from control group (2.53±1.416 ng/ml/hr) except in malignant hypertension (6.09±2.042, p 0.1). It is suggested that renin-angiotensin system plays a predominant role in the pathogenesis of malignant hypertension and in hypertension of chronic renal failure, though sodium retention is also contributing factor. PRA variation in essential hypertension does not appear to be associated with any consistent change in Na-volume status, suggesting the existence of another mechanism in the genesis of hypertension and PRA variation.

Capturing the dynamics of systemic Renin-Angiotensin-Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs.

Science.gov (United States)

Mochel, J P; Peyrou, M; Fink, M; Strehlau, G; Mohamed, R; Giraudel, J M; Ploeger, B; Danhof, M

2013-04-01

In dogs, activation of the Renin-Angiotensin-Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long-term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin-converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low-sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC of plasma renin activity (+90%), angiotensin I (+43%), and AII (-53%) were found between benazepril and placebo-treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs. © 2012 Blackwell Publishing Ltd.

Expression of genes of the cardiac and renal renin-angiotensin systems in preterm piglets: is this system a suitable target for therapeutic intervention?

Science.gov (United States)

Kim, Eleanor; Eiby, Yvonne; Lumbers, Eugenie; Boyce, Amanda; Gibson, Karen; Lingwood, Barbara

2015-10-01

The newborn circulating, cardiac and renal renin-angiotensin systems (RASs) are essential for blood pressure control, and for cardiac and renal development. If cardiac and renal RASs are immature this may contribute to cardiovascular compromise in preterm infants. This study measured mRNA expression of cardiac and renal RAS components in preterm, glucocorticoid (GC) exposed preterm, and term piglets. Renal and cardiac RAS mRNA levels were measured using real-time polymerase chain reaction (PCR). Genes studied were: (pro)renin receptor, renin, angiotensinogen, angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R). All the genes studied were expressed in the kidney; neither renin nor AT2R mRNA were detected in the heart. There were no gestational changes in (pro)renin receptor, renin, ACE or AT1R mRNA levels. Right ventricular angiotensinogen mRNA levels in females were lower in preterm animals than at term, and GC exposure increased levels in male piglets. Renal angiotensinogen mRNA levels in female term piglets were lower than females from both preterm groups, and lower than male term piglets. Left ventricular ACE2 mRNA expression was lower in GC treated preterm piglets. Renal AT2R mRNA abundance was highest in GC treated preterm piglets, and the AT1R/AT2R ratio was increased at term. Preterm cardiac and renal RAS mRNA levels were similar to term piglets, suggesting that immaturity of these RASs does not contribute to preterm cardiovascular compromise. Since preterm expression of both renal and cardiac angiotensin II-AT1R is similar to term animals, cardiovascular dysfunction in the sick preterm human neonate might be effectively treated by agents acting on their RASs. © The Author(s), 2015.

Hyperpotassemia and bradycardia in a bedridden elderly woman with selective hypoaldosteronism associated with low renin activity.

Science.gov (United States)

Inada, Mitsuo; Iwasaki, Keiko; Imai, Chihiro; Hashimoto, Satoshi

2010-01-01

A bedridden 85-year-old woman had hyperpotassemia (7.7 mEq/L) and bradycardia (30/min). Endocrinologic findings revealed a decrease in the renin-aldosterone system and normal adrenoglucocorticoid function. The results were consistent with the abnormalities seen in selective hypoaldosteronism with low renin activity. In addition, 9 of 11 patients, selected randomly from 72 bedridden elderly patients with normal serum sodium and potassium levels in our hospital, had diminished plasma renin activity (PRA) and plasma aldosterone concentration (PAC). The present patient was prescribed nonsteroidal anti-inflammatory drug (NSAID). NSAID reduces renal potassium excretion through the inhibition of renal prostaglandin synthesis. Therefore, the use of NSAID in bedridden elderly patients might intensify the underlying asymptomatic hypoaldosteronism and cause life-threatening hyperpotassemia.

Renin-aldosterone-sodium profiling in hypertensive Filipinos. Pt. 2

Energy Technology Data Exchange (ETDEWEB)

Guevara, R.; Torres, J. Jr; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

1981-10-01

Plasma renin activity determination by radioimmunoassay as profiling technique is a useful guide for more rational and precise treatment of hypertension. Statistical nomograms are developed for normals, essential hypertension, diabetic hypertension, renal diseases, renal disease and dialysis, normal pregnancy, toxemic pregnancy and contraceptive pill users with and without hypertension.

Normotensive sodium loading in conscious dogs: Regulation of renin secretion during beta receptor blockade

DEFF Research Database (Denmark)

Bie, Peter; Mølstrøm, Simon; Wamberg, Søren

2009-01-01

Cl (20 micromol/kg/min for 180 min, NaLoad) during regular or low-sodium diet (0.03 mmol/kg/d, LowNa) with and without metoprolol (2 mg/kg plus 0.9 mg/kg/h). Vasopressin V2 receptors were blocked by Otsuka compound OPC31260 to facilitate clearance measurements. Body fluid volume was maintained by servo-controlled...... that in this setting, renin secretion and renin-dependent sodium excretion are controlled by via the renal nerves and therefore eliminated or reduced by blocking the action of norepinephrine on the juxtaglomerular cells with the beta1-receptor antagonist metoprolol. This was tested in conscious dogs by infusion of Na...... irrespective of diet. In conclusion, PRC depended on dietary sodium and beta1-adrenergic control as expected; however, the acute sodium-driven decrease in PRC at constant MAP and GFR was unaffected by beta1-receptor blockade demonstrating that renin may be regulated without changes in MAP, GFR, or beta1...

Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement

DEFF Research Database (Denmark)

Campbell, Duncan J; Nussberger, Juerg; Stowasser, Michael

2009-01-01

into focus the differences in information provided by activity assays and immunoassays for renin and prorenin measurement and has drawn attention to the need for precautions to ensure their accurate measurement. CONTENT: Renin activity assays and immunoassays provide related but different information...... provided by these assays and of the precautions necessary to ensure their accuracy....

Renin-aldosterone-sodium profiling in hypertensive Filipinos. Pt. 2

International Nuclear Information System (INIS)

Guevara, R.; Torres, J. Jr; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

1981-01-01

Plasma renin activity determination by radioimmunoassay as profiling technique is a useful guide for more rational and precise treatment of hypertension. Statistical nomograms are developed for normals, essential hypertension, diabetic hypertension, renal diseases, renal disease and dialysis, normal pregnancy, toxemic pregnancy and contraceptive pill users with and without hypertension. (orig.) [de

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

Science.gov (United States)

Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Bivens, Tiffany B; Adams-Huet, Beverley; Levine, Benjamin D; Fu, Qi

2013-01-01

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)−1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)−1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)−1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)−1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin–angiotensin–aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).

Science.gov (United States)

Schroten, Nicolas F; Damman, Kevin; Hemmelder, Marc H; Voors, Adriaan A; Navis, Gerjan; Gaillard, Carlo A J M; van Veldhuisen, Dirk J; Van Gilst, Wiek H; Hillege, Hans L

2015-05-01

We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals. Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007). Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction. Copyright © 2015 Mosby, Inc. All rights reserved.

Renin-aldosterone-sodium profiling in normal Filipinos. Pt. 1

International Nuclear Information System (INIS)

Guevara, R.; Torres, J. Jr.; Abundo, H.P.; Perez, A.P.; Ochoa, W.K.

1981-01-01

Plasma renin activity determination by radioimmunoassay is feasible, accurate, reproducible and reliable. This profiling technic is a very useful guide for more rational and precise treatment of the hypertensive state, but even when profiling cannot be done, statistical nomograms can be useful, just as well, as a guide in the treatment of hypertewnsion. (orig.) [de

Aliskiren, a Direct Renin Inhibitor, Improves Vascular Endothelial Function in Patients on Hemodialysis Independent of Antihypertensive Effect ∼ a Pilot Study∼

Directory of Open Access Journals (Sweden)

Hidekazu Moriya

2013-05-01

Full Text Available Aims: Aliskiren inhibits the first step in the renin-angiotensin system (RAS and recently has been shown to modulate vascular diseases via RAS-dependent and independent pathways. This study aimed to determine the effect of aliskiren-associated direct renin inhibition on endothelial function in patients on hemodialysis via flow-mediated dilatation (FMD and platelet-derived microparticles (PDMP, as biomarkers of atherosclerosis. Methods: A 12-week prospective study was performed with 24 patients on hemodialysis who were administered 150 mg orally aliskiren once daily for 12 weeks. Results: No significant difference were observed between pre-dialysis, home, and weekly averaged blood pressure at baseline and at 12 weeks (151.5 ± 8.5/80.9 ± 12.9 mmHg vs 150.3 ± 15.3/78.9 ± 21.2 mmHg, 151.4 ± 9.7/82.3 ± 14.7 mmHg vs 151.2 ± 17.7/81.4 ± 10.6 mmHg, and 156.0 ± 18.3/81.9 ± 9.4 mmHg vs 152.5 ± 18.9/81.7 ± 12.3 mmHg, respectively. FMD significantly increased from 2.54% ± 1.45% at baseline to 3.11% ± 1.37% at 12 weeks (P = 0.0267, and PDMP significantly decreased from 13.9 ± 5.8 U/mL at baseline to 10.9 ± 4.5 U/mL at 12 weeks (P = 0.0002. Conclusion: Aliskiren improved vascular endothelial function and platelet-endothelium activation in patients on hemodialysis independent of antihypertensive effect.

The role of the renin-angiotensin system in the development of insulin resistance in skeletal muscle.

Science.gov (United States)

Henriksen, Erik J; Prasannarong, Mujalin

2013-09-25

The canonical renin-angiotensin system (RAS) involves the initial action of renin to cleave angiotensinogen to angiotensin I (ANG I), which is then converted to ANG II by the angiotensin converting enzyme (ACE). ANG II plays a critical role in numerous physiological functions, and RAS overactivity underlies many conditions of cardiovascular dysregulation. In addition, ANG II, by acting on both endothelial and myocellular AT1 receptors, can induce insulin resistance by increasing cellular oxidative stress, leading to impaired insulin signaling and insulin-stimulated glucose transport activity. This insulin resistance associated with RAS overactivity, when coupled with progressive ß-cell dysfunction, eventually leads to the development of type 2 diabetes. Interventions that target RAS overactivity, including ACE inhibitors, ANG II receptor blockers, and, most recently, renin inhibitors, are effective both in reducing hypertension and in improving whole-body and skeletal muscle insulin action, due at least in part to enhanced Akt-dependent insulin signaling and insulin-dependent glucose transport activity. ANG-(1-7), which is produced from ANG II by the action of ACE2 and acts via Mas receptors, can counterbalance the deleterious actions of the ACE/ANG II/AT1 receptor axis on the insulin-dependent glucose transport system in skeletal muscle. This beneficial effect of the ACE2/ANG-(1-7)/Mas receptor axis appears to depend on the activation of Akt. Collectively, these findings underscore the importance of RAS overactivity in the multifactorial etiology of insulin resistance in skeletal muscle, and provide support for interventions that target the RAS to ameliorate both cardiovascular dysfunctions and insulin resistance in skeletal muscle tissue. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Radioimmunoassay for determination of blood aldosterone and renin in the diagnosis of some forms of arterial hypertension

International Nuclear Information System (INIS)

Khamidov, R.I.; Khalmuratova, R.A.; Sattarova, F.K.

1987-01-01

Aldosterone concentration and renin activity in the blood from the ulnar, inferior cava veins at the level of the 12th thoracic vertebra, the left and right renal veins were studied in 60 patients with arterial hypertension by means of a radioimmunoassay kits (France). The patients were divided into 4 groups: with primary and idiopathic hyperaldosteronism, renal-parenchymatous and essential arterial hypertension. The diagnosis of primary and idiopathic hyperaldosteronism was also confirmed by low blood renin activity. Renin activity in the peripheral venous blood was considerably elevated in renal-parenchymatous arterial hypertension and was normal in essential hypertension. Aldosterone concentration in the blood from the vena cava inferior and renal veins was 1.6-2-fold as high on the affected side as on the contralateral one

Renin-Angiotensin System in Diabetes.

Science.gov (United States)

Rein, Johannes; Bader, Michael

2017-11-17

The renin-angiotensin system (RAS) has two different axes, the classical one with the effector peptide angiotensin II and the new one with the effector peptide angiotensin (1-7). Both peptides have been shown to be involved in the pathogenesis of diabetes mellitus and its consequences, nephropathy, retinopathy and cardiomyopathy in animal models and patients. In diabetes, angiotensin II acts mostly deleterious and angiotensin (1-7) protective. In this review we summarize the knowledge about the role of the different RAS axes in diabetes mellitus and the use of drugs interfering with the RAS in the therapy of the disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Renin secretion and total body sodium: Pathways of integrative control

DEFF Research Database (Denmark)

Bie, Peter; Damkjaer, Mads

2009-01-01

to a spring/shock absorber set-up: Non-adaptive RAAS functions determine the new steady state position while TGF controls the rate of change. Recruitment of renin-secreting cells during sustained stimulation may be essential for chronic adaptation, although details of this afferent arteriolar cell plasticity...

Cortisol-induced inhibition of ovine renin and aldosterone responses to hypotension

International Nuclear Information System (INIS)

Wood, C.E.; Silbiger, J.

1987-01-01

Previous studies from this laboratory have demonstrated that in preterm fetal sheep increases in plasma cortisol (F) concentration equal in amplitude to fetal F stress responses suppress plasma renin activity (PRA). The purpose of this study was to investigate the possibility that this negative interaction exists in adult sheep. Cortisol was measured by radioimmunoassay. Five conscious ewes with chronically prepared carotid arterial loops were infused intravenously with F or vehicle for 5 h. One hour after the end of F or vehicle infusion, renin secretion was stimulated by hypotension produced by infusion of sodium nitroprusside. F infusion increased plasma F; during vehicle infusion plasma F did not change. F infusion decreased hematocrit from 29 +/- 2 to 26 +/- 1%. Basal PRA in vehicle- and F-infused groups were 0.4 +/- 0 and 0.2 +/- 0.1 ng angiotensin I-ml -1 -h -1 and did not change. In vehicle-infused ewes, PRA increased from 0.4 +/- 0 to 4.6 +/- 0.4 and plasma aldosterone from 26.0 +/- 1.0 to 173.1 +/- 21.8 pg/ml, while in F-infused ewes, PRA increased from 0.2 +/- 1 to 3.3 +/- 0.4 ng angiotensin I-ml -1 -h -1 and aldosterone from 25.0 +/- 0 to 48.2 +/- 23.2 pg/ml, significantly smaller responses. These results suggest that repeated stress may modulate the responses of the renin-angiotensin system in this species

Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial.

Science.gov (United States)

McMullan, Ciaran J; Borgi, Lea; Fisher, Naomi; Curhan, Gary; Forman, John

2017-05-08

Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting. In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping. Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m 2 ) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group ( P =0.83), -4 (-16 to 9) in the allopurinol group ( P =0.32), and 1 (-21 to 17) in the placebo group ( P =0.96), with no significant treatment effect ( P =0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid ( P =0.43), -0.4±6.1 with allopurinol ( P =0.76), and 0.5±6.0 with placebo ( P =0.65); there was no significant treatment effect ( P =0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively. In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney

High-intensity interval training has beneficial effects on cardiac remodeling through local renin-angiotensin system modulation in mice fed high-fat or high-fructose diets.

Science.gov (United States)

de Oliveira Sá, Guilherme; Dos Santos Neves, Vívian; de Oliveira Fraga, Shyrlei R; Souza-Mello, Vanessa; Barbosa-da-Silva, Sandra

2017-11-15

HIIT (high-intensity interval training) has the potential to reduce cardiometabolic risk factors, but the effects on cardiac remodeling and local RAS (renin-angiotensin system) in mice fed high-fat or high-fructose diets still need to be fully addressed. Sixty male C57BL/6 mice (12weeks old) were randomly divided into three groups, control (C), High-fat (HF), or High-fructose diet (HRU) and were monitored for eight weeks before being submitted to the HIIT. Each group was randomly assigned to 2 subgroups, one subgroup was started on a 12-week HIIT protocol (T=trained group), while the other subgroup remained non-exercised (NT=not-trained group). HIIT reduced BM and systolic blood pressure in high-fat groups, while enhanced insulin sensitivity after high-fat or high-fructose intake. Moreover, HIIT reduced left ventricular hypertrophy in HF-T and HFRU-T. Notably, HIIT modulated key factors in the local left ventricular renin-angiotensin-system (RAS): reduced protein expression of renin, ACE (Angiotensin-converting enzyme), and (Angiotensin type 2 receptor) AT2R in HF-T and HFRU-T groups but reduced (Angiotensin type 1 receptor) AT1R protein expression only in the high-fat trained group. HIIT modulated ACE2/Ang (1-7)/Mas receptor axis. ACE2 mRNA gene expression was enhanced in HF-T and HFRU-T groups, complying with elevated Mas (Mas proto-oncogene, G protein-coupled receptor) receptor mRNA gene expression after HIIT. This study shows the effectiveness of HIIT sessions in producing improvements in insulin sensitivity and mitigating LV hypertrophy, though hypertension was controlled only in the high-fat-fed submitted to HIIT protocol. Local RAS system in the heart mediates these findings and receptor MAS seems to play a pivotal role when it comes to the amelioration of cardiac structural and functional remodeling due to HIIT. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.

Science.gov (United States)

Fang, Hui; Deng, Mokan; Zhang, Linlin; Lu, Aihua; Su, Jiahui; Xu, Chuanming; Zhou, Li; Wang, Lei; Ou, Jing-Song; Wang, Weidong; Yang, Tianxin

2018-05-30

Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) alone or in conjunction with a PRR decoy inhibitor PRO20 (500 μg/kg/d via 3 s.c. injections). The AO rat model exhibited severe proteinuria, tubular necrosis, and interstitial fibrosis, oxidative stress, inflammation, accompanied by elevated urinary N-acetyl-beta-D-glucosaminidase activity and urinary β2-microglobulin secretion, all of which were significantly attenuated by PRO20. Urinary and renal levels of renin, angiotensinogen (AGT), and Ang II were elevated by AO and suppressed by PRO20, contrasting to largely unaltered plasma levels of the RAS parameters. The AO model also showed increased renal expression of full-length PRR and soluble PRR (sPRR) and urinary excretion of sPRR. Taken together, we conclude that PRR antagonism with PRO20 alleviates AO-induced nephropathy via inhibition of intrarenal RAS.

Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension.

Science.gov (United States)

Boshra, Vivian; Abbas, Amr M

2017-07-26

Renovascular hypertension (RVH) is a result of renal artery stenosis, which is commonly due to astherosclerosis. In this study, we aimed to clarify the central and peripheral effects of ghrelin on the renin-angiotensin system (RAS) in a rat model of RVH. RVH was induced in rats by partial subdiaphragmatic aortic constriction. Experiment A was designed to assess the central effect of ghrelin via the intracerebroventricular (ICV) injection of ghrelin (5 μg/kg) or losartan (0.01 mg/kg) in RVH rats. Experiment B was designed to assess the peripheral effect of ghrelin via the subcutaneous (SC) injection of ghrelin (150 μg/kg) or losartan (10 mg/kg) for 7 consecutive days. Mean arterial blood pressure (MAP), heart rate, plasma renin activity (PRA), and oxidative stress markers were measured in all rats. In addition, angiotensin II receptor type 1 (AT1R) concentration was measured in the hypothalamus of rats in Experiment B. RVH significantly increased brain AT1R, PRA, as well as the brain and plasma oxidative stress. Either SC or ICV ghrelin or losartan caused a significant decrease in MAP with no change in the heart rate. Central ghrelin or losartan caused a significant decrease in brain AT1R with significant alleviation of the brain oxidative stress. Central ghrelin caused a significant decrease in PRA, whereas central losartan caused a significant increase in PRA. SC ghrelin significantly decreased PRA and plasma oxidative stress, whereas SC losartan significantly increased PRA and decreased plasma oxidative stress. The hypotensive effect of ghrelin is mediated through the amelioration of oxidative stress, which is induced by RAS centrally and peripherally.

Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats.

Science.gov (United States)

Frantz, Eliete Dalla Corte; Medeiros, Renata Frauches; Giori, Isabele Gomes; Lima, Juliana Bittencourt Silveira; Bento-Bernardes, Thais; Gaique, Thaiane Gadioli; Fernandes-Santos, Caroline; Fernandes, Tiago; Oliveira, Edilamar Menezes; Vieira, Carla Paulo; Conte-Junior, Carlos Adam; Oliveira, Karen Jesus; Nobrega, Antonio Claudio Lucas

2017-09-01

What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l -1 ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day -1 , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and

Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

DEFF Research Database (Denmark)

Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey

2012-01-01

, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review...... the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS...

A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice.

Science.gov (United States)

Jackson, Kristy L; Marques, Francine Z; Watson, Anna M D; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Morris, Brian J; Charchar, Fadi J; Davern, Pamela J; Head, Geoffrey A

2013-10-01

Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.

Effect of Renin-Angiotensin Blockers on Left Ventricular Remodeling in Severe Aortic Stenosis.

Science.gov (United States)

Goh, Serene Si-Ning; Sia, Ching-Hui; Ngiam, Nicholas Jinghao; Tan, Benjamin Yong-Qiang; Lee, Poay Sian; Tay, Edgar Lik-Wui; Kong, William Kok-Fai; Yeo, Tiong Cheng; Poh, Kian-Keong

2017-06-01

Studies have shown that medical therapy with renin-angiotensin blockers (RABs) may benefit patients with aortic stenosis (AS). However, its use and efficacy remains controversial, including in patients with low flow (LF) with preserved left ventricular ejection fraction (LVEF). We examined the effects of RAB use on LV remodeling in patients with severe AS with preserved LVEF, analyzing the differential effects in patients with LF compared with normal flow (NF). This is a retrospective study of 428 consecutive subjects from 2005 to 2014 with echocardiographic diagnosis of severe AS and preserved LVEF. Clinical and echocardiographic parameters were systematically collected and analyzed. Two hundred forty-two (57%) patients had LF. Sixty-four LF patients (26%) were treated with RAB. Patients on RAB treatment had a higher incidence of hyperlipidemia (69% vs 44%) and diabetes mellitus (53% vs 34%). Severity of AS in terms of valve area, transvalvular mean pressure gradient, and aortic valve resistance were similar between both groups as was the degree of LV diastolic function. The RAB group demonstrated significantly lower LV mass index with a correspondingly lower incidence of concentric LV hypertrophy. Regardless of the duration of RAB therapy, patients had increased odds of having a preserved LV mass index compared with those without RAB therapy. In conclusion, RAB therapy may be associated with less LV pathological remodeling and have a role in delaying patients from developing cardiovascular complications of AS. Copyright © 2017 Elsevier Inc. All rights reserved.

Severe hypoglycaemia during pregnancy in women with type 1 diabetes: possible role of renin-angiotensin system activity?

DEFF Research Database (Denmark)

Nielsen, L Ringholm; Pedersen-Bjergaard, U; Thorsteinsson, B

2009-01-01

AIMS: To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM). METHODS: Severe hypoglycaemic events the year preceding pregnancy were recorded...... retrospectively in 107 consecutive pregnant women with T1DM. Events during pregnancy were recorded prospectively. Measurements of ACE, renin and angiotensinogen were determined at 8, 14, 21, 27 and 33 weeks and postpartum. RESULTS: The rate of severe hypoglycaemia was 1.1 and 5.3 events/patient-year the year...... preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks. CONCLUSIONS: In early...

Emerging drugs which target the renin-angiotensin-aldosterone system.

Science.gov (United States)

Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

2011-12-01

The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

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Indu Dhar

Full Text Available The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs. Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs. HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH, proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

Science.gov (United States)

Dhar, Indu; Dhar, Arti; Wu, Lingyun; Desai, Kaushik M

2013-01-01

The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.

AFM plough YBCO micro bridges: substrate effects

CSIR Research Space (South Africa)

Elkaseh, A

2009-04-01

Full Text Available AFM nanolithography was used as a novel cutting technique to define micro-size YBCO superconducting constrictions. Researchers studied the substrate effects on MgO and STO substrates and showed that the observed Shapiro steps from the bridges on STO...

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

Directory of Open Access Journals (Sweden)

Yavuz Beyazit

2011-01-01

Full Text Available Local hematopoietic bone marrow (BM renin-angiotensin system (RAS affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II, the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R, has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

Dual Blockade of the Renin-angiotensin-aldosterone System in Type 2 Diabetic Kidney Disease

Directory of Open Access Journals (Sweden)

Yan-Huan Feng

2016-01-01

Full Text Available Objective: To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system (RAAS among patients with type 2 diabetic kidney disease. Data Sources: We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use of monotherapy, without applying any language restrictions. Keywords for the searches included "diabetic nephropathy," "chronic kidney disease," "chronic renal insufficiency," "diabetes mellitus," "dual therapy," "combined therapy," "dual blockade," "renin-angiotensin system," "angiotensin-converting enzyme inhibitor," "angiotensin-receptor blocker," "aldosterone blockade," "selective aldosterone blockade," "renin inhibitor," "direct renin inhibitor," "mineralocorticoid receptor blocker," etc. Study Selection: The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results: Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin II receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions: Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an

Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors

DEFF Research Database (Denmark)

Pedersen-Bjergaard, Ulrik

2009-01-01

this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire...... targets and thereby open for prevention of severe hypoglycaemia. Furthermore, subjects with elevated renin-angiotensin system activity and a high rate of severe hypoglycaemia might benefit from pharmacological blockade of the renin-angiotensin system by ACE inhibitors or angiotensin II receptor blockers...

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

Science.gov (United States)

Mao, Caiping; Liu, Rong; Bo, Le; Chen, Ningjing; Li, Shigang; Xia, Shuixiu; Chen, Jie; Li, Dawei; Zhang, Lubo; Xu, Zhice

2013-07-01

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

Substrate Effects in Wideband SiGe HBT Mixer Circuits

DEFF Research Database (Denmark)

Johansen, Tom Keinicke; Vidkjær, Jens; Krozer, Viktor

2005-01-01

are also applied to predict short distance substrate coupling effects. Simulation results using extracted equivalent circuit models and substrate coupling networks are compared with experimental results obtained on a wideband mixer circuit implemented in a 0.35 μm, 60 GHz ft SiGe HBT BiCMOS process.......In this paper, the influence from substrate effects on the performance of wideband SiGe HBT mixer circuits is investigated. Equivalent circuit models including substrate networks are extracted from on-wafer test structures and compared with electromagnetic simulations. Electromagnetic simulations...

Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

OpenAIRE

Ramachandran, Vasudevan; Ismail, Patimah; Stanslas, Johnson; Shamsudin, Norashikin

2009-01-01

Abstract Background The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS...

Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice.

Science.gov (United States)

Fukushima, Arata; Kinugawa, Shintaro; Takada, Shingo; Matsumoto, Junichi; Furihata, Takaaki; Mizushima, Wataru; Tsuda, Masaya; Yokota, Takashi; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

2016-05-15

Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels

NARCIS (Netherlands)

Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II

Radioimmunologic analysis of the state of the renin-angiotensin-aldosterone system in arterial hypertension

International Nuclear Information System (INIS)

Slavnov, V.N.; Yakovlev, A.A.; Gandzha, T.I.; Yugrinov, O.G.

1986-01-01

For 110 patients having various forms of arterial hypertension (hypertension, aldersteronoma, phaeochromocytoma, corticosteroma) the parameters of the system renin-angiotensin-aldosterone (RAA) were measured. Basal values of aldosterone and renin activity in blood were determined as well as their concentration in blood taken from the vena cava inferior, renal and adrenal veins during selective renography. The 24-hours rhythm of the hormones in the blood, the reaction of the glomerular zone of the adrenal cortex and the juxtaglomerular renal system under acute lasix stress was evaluated. It was found, that the system RAA is disturbed in all patients with arterial hypertension. This is indicated by changes of aldosterone concentration, renin activity in peripheral blood and in the blood from the vena cava inferior, renal and adrenal veins, the 24-hour rhythm of their concentrations in serum and the reaction to acute lasix stress. The radioimmunoassays of quantitative parameters of the RAA system are decisive for the differential diagnostics of hypertension and suprarenomas connected with a hypertension syndrome. They facilitate a rational choice of the hypertension therapy and the daily distribution of the medicaments for patients with hypertension. The radioimmunoassays can be used for checking the efficiency of medicaments and surgery. (author)

Expressions of renin, angiotensin II and aldosterone in patients with viral hepatitis or hepatic cirrhosis

International Nuclear Information System (INIS)

Huo Ying; Zhu Yalin; Liu Yun

2008-01-01

Objective: To explore the changes of renin, angiotensin and aldosterone system in patients with hepatic disorders. Methods: Plasma renin activity (PRA), AT-II and Ald levels were measured with RIA in 31 patients with viral hepatitis, 35 patients with hepatic cirrhosis and 38 controls. Results: The levels of PRA, AT-II and Ald in patients with viral hepatitis were slightly but non-significantly higher than those in controls (P>0.05). The levels of PRA, AT-II and Ald in patients with cirrhosis were significantly higher than those in controls (P<0.01). Conclusion: RAAS was activated during progression of hepatic disorders and participated in the development of hepatic fibrosis. (authors)

The Relevance of the Renin-Angiotensin System in the Development of Drugs to Combat Preeclampsia

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Norikazu Ueki

2015-01-01

Full Text Available Preeclampsia is a hypertensive disorder that occurs during pregnancy. It has an unknown etiology and affects approximately 5–8% of pregnancies worldwide. The pathophysiology of preeclampsia is not yet known, and preeclampsia has been called “a disease of theories.” The central symptom of preeclampsia is hypertension. However, the etiology of the hypertension is unknown. In this review, we analyze the molecular mechanisms of preeclampsia with a particular focus on the pathogenesis of the hypertension in preeclampsia and its association with the renin-angiotensin system. In addition, we propose potential alternative strategies to target the renin-angiotensin system, which is enhanced during pregnancy.

Combined effects of aging and inflammation on renin-angiotensin system mediate mitochondrial dysfunction and phenotypic changes in cardiomyopathies.

Science.gov (United States)

Burks, Tyesha N; Marx, Ruth; Powell, Laura; Rucker, Jasma; Bedja, Djahida; Heacock, Elisa; Smith, Barbara J; Foster, D Brian; Kass, David; O'Rourke, Brian; Walston, Jeremy D; Abadir, Peter M

2015-05-20

Although the effects of aging and inflammation on the health of the cardiac muscle are well documented, the combined effects of aging and chronic inflammation on cardiac muscle are largely unknown. The renin-angiotensin system (RAS) has been linked independently to both aging and inflammation, but is understudied in the context of their collective effect. Thus, we investigated localized cardiac angiotensin II type I and type II receptors (AT(1)R, AT(2)R), downstream effectors, and phenotypic outcomes using mouse models of the combination of aging and inflammation and compared it to a model of aging and a model of inflammation. We show molecular distinction in the combined effect of aging and inflammation as compared to each independently. The combination maintained an increased AT(1)R:AT(2)R and expression of Nox2 and exhibited the lowest activity of antioxidants. Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed inflammatory conditions as premature aging, but they are, in fact, molecularly distinct. Moreover, treatment with an AT(1)R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation.

Science.gov (United States)

Kanda, Atsuhiro; Ishizuka, Erdal Tan; Shibata, Atsushi; Matsumoto, Takahiro; Toyofuku, Hidekazu; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

2017-06-16

The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines. Moreover, we developed a novel single-strand RNAi agent, proline-modified short hairpin RNA directed against human and mouse (P)RR [(P)RR-PshRNA], and we determined its safety and efficacy in vitro and in vivo. Application of (P)RR-PshRNA in mice caused significant amelioration of acute (uveitic) and chronic (diabetic) models of ocular inflammation with no apparent adverse effects. Our findings demonstrate the significant implication of RAPS in the pathogenesis of human uveitis and the potential usefulness of (P)RR-PshRNA as a therapeutic agent to reduce ocular inflammation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The renin-angiotensin system and aging in the kidney

OpenAIRE

Yoon, Hye Eun; Choi, Bum Soon

2014-01-01

Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and function...

The role of renin angiotensin system in retinal inflammation

OpenAIRE

Zhu, Tong

2017-01-01

Purpose: Retinopathy of prematurity (ROP) is the main cause of vision loss and blindness in children, and is replicated and intensively studied in rodent models of oxygen-induced retinopathy (OIR). One signature feature of ROP is retinal neovascularization, which is also present in patients with proliferative diabetic retinopathy (PDR). Inflammation is another feature in ROP and PDR. In both diseases, the renin angiotensin system (RAS) is dysregulated, and blockade of RAS via angiotensin II (...

Radiolabelled substrates for studying biological effects of trace contaminants

International Nuclear Information System (INIS)

1975-01-01

A programme of coordinated isotopic tracer-aided investigations of the biological side-effects of foreign chemical residues in food and agriculture, initiated in 1973, was reviewed. The current status of representative investigations from the point of view of techniques and priorities was assessed. Such investigations involved radioactive substrates for studying DNA injury and its repair; 14 C-labelled acetylcholine as substrate for measuring enzyme inhibition due to the presence of, or exposure to, anticholinesteratic contaminants; radioactive substrates as indication of side-effects in non-target organisms and of their comparative susceptibilities; radioactive substrates as indicators of persistence or biodegradability of trace contaminants of soil or water; and labelled pools for studying the biological side-effects of trace contaminants. Priorities were identified

Multilocus analyses of renin-angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects

NARCIS (Netherlands)

Ge, Dongliang; Zhu, Haidong; Huang, Ying; Treiber, Frank A.; Harshfield, Gregory A.; Snieder, Harold; Dong, Yanbin

The renin-angiotensin-aldosterone system (RAAS) is a proteolytic cascade that regulates and maintains blood pressure (BP). This study aimed to explore the interactive and integrative effects of multiple RAAS polymorphisms on BP at rest and during behavioral stress in a normotensive population. A

Investigating the association of vitamin D with blood pressure and the renin-angiotensin-aldosterone system in hypertensive subjects: a cross-sectional prospective study.

Science.gov (United States)

Cremer, Antoine; Tambosco, Chloé; Corcuff, Jean-Benoît; Boulestreau, Romain; Gaillard, Prune; Lainé, Marion; Papaioannou, Georgios; Gosse, Philippe

2018-02-01

The hypothesis that vitamin D (25(OH)D) insufficiency plays a role in occurring of various disease has led to a rise in requests of dosages and to an increase of health-care costs. 25(OH)D insufficiency is associated with increased risk of cardiovascular disease and hypertension in many studies. Animal studies demonstrated that 25(OH)D insufficiency activates renin angiotensin system but corresponding humans data are limited. The aim of the study was to document relationship between 25(OH)D, blood pressure, and renin angiotensin system in hypertensive subjects. In all, 248 hypertensive individuals, 46.8 years (±14), were hospitalized for an etiological assessment of hypertension in this cross-sectional study over two calendar years. 25(OH)D, plasma renin activity, and aldosterone were determined in stringent conditions and blood pressure was measure. Statistical analyses were carried out to analyze the association between 25(OH)D, blood pressure, and renin angiotensin system using linear and logistic regressions with adjustments on relevant variables. In all, 80% of the studied population had a 25(OH)D insufficiency. There were no significant association between 25(OH)D and levels of systolic or diastolic blood pressure, plasma renin activity, and aldosterone whatever the statiscal method used after adjustment. 25(OH)D is not associated with blood pressure and renin angiontensin component in hypertensive subjects. These results corroborate the interventional studies which are for a large majority negatives. A new definition of the 25(OH)D insufficiency in general population is necessary.

Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.

Science.gov (United States)

Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany; Arjunan, Pachiappan; Martin, Pamela; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya P

2018-02-14

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

Functional interactions between 7TM receptors in the renin-angiotensin system--dimerization or crosstalk?

DEFF Research Database (Denmark)

Lyngsø, Christina; Erikstrup, Niels; Hansen, Jakob L

2008-01-01

. The importance of the RAS is clearly emphasised by the widespread use of drugs targeting this system in clinical practice. These include, renin inhibitors, angiotensin II receptor type I blockers, and inhibitors of the angiotensin converting enzyme. Some of the important effectors within the system are 7...... be important for receptor function, and in the development of cardiovascular diseases. This is very significant, since "dimers" may provide pharmacologists with novel targets for improved drug therapy. However, we know that 7TM receptors can mediate signals as monomeric units, and so far it has been very......The Renin-Angiotensin System (RAS) is important for the regulation of cardiovascular physiology, where it controls blood pressure, and salt- and water homeostasis. Dysregulation of RAS can lead to severe diseases including hypertension, diabetic nephropathy, and cardiac arrhythmia, and -failure...

Normotensive sodium loading in normal man: Regulation of renin secretion during beta-receptor blockade

DEFF Research Database (Denmark)

Mølstrøm, Simon; Larsen, Nils Heden; Simonsen, Jane Angel

2008-01-01

and renal excretion during slow saline loading at constant plasma sodium con-centration (Na-loading: 12 micromol Na(+) kg(-1) min(-1) for 4 h). Normal subjects were studied on low-sodium intake with and without beta1-adrenergic blockade by metoprolol. Metoprolol per se reduced RAAS activity as expected. Na......Saline administration may change renin system (RAAS) activity and sodium excretion at constant mean arterial pressure (MAP). We hypothesized that such responses are elicited mainly by renal sympathetic nerve activity by beta1-receptors (beta1-RSNA), and tested the hypothesis by studying RAAS......-loading decreased plasma renin (PRC) by 1/3, AngII by 1/2, and aldosterone (pAldo) by 2/3, (all psodium excretion increased indistinguishably with and without metoprolol (16+/-2 to 71...

Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

Science.gov (United States)

Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

2017-05-01

Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

Direct renin inhibitors – new approaches in the treatment of patients with arterial hypertension associated with obesity, diabetes mellitus, menopause and kidneys’ disorders

OpenAIRE

Syvolap, V. V.; Gerasko, M. P.

2013-01-01

In this review composed on the data of multicentred randomized investigations the advantages of direct renin inhibitors for patients with arterial hypertension are discussed. The prospects of using direct renin inhibitors in the cases of arterial hypertension associated with obesity, diabetes mellitus, menopause and kidneys’ disorders are studied.

The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor

Directory of Open Access Journals (Sweden)

Rene Baudrand

2018-02-01

Full Text Available A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH. Classically, the individual causes of LRH have been considered to be rare diseases; however, recent advances suggest that there are milder and “non-classical” variants of many LRH-inducing conditions. In this regard, our understanding of the underlying genetics and mechanisms accounting for LRH, and therefore, potentially the pathogenesis of a large subset of essential hypertension, is evolving. This review will discuss the potential causes of LRH, with a focus on implicated genetic mechanisms, the expanding recognition of non-classical variants of conditions that induce LRH, and the role of the mineralocorticoid receptor in determining this phenotype.

Skeletal muscle wasting: new role of nonclassical renin-angiotensin system.

Science.gov (United States)

Cabello-Verrugio, Claudio; Rivera, Juan C; Garcia, Dominga

2017-05-01

Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance. Recent studies have shown that angiotensin (1-7) [Ang-(1-7)] - a vasoactive peptide of the nonclassical axis in the renin-angiotensin system (RAS) - and its Mas receptor are expressed in skeletal muscle. Ang-(1-7), through its Mas receptor, prevents or diminishes deleterious effects induced by skeletal muscle disease or injury. Specifically, the Ang-(1-7)-Mas receptor axis modulates molecular mechanisms involved in muscle mass regulation, such as the ubiquitin proteasome pathway, the insulin-like growth factor type 1/Akt (protein kinase B) pathway, or myonuclear apoptosis, and also inflammation and fibrosis pathways. Although further research into this topic and the possible side effects of Ang-(1-7) is necessary, these findings are promising, and suggest that the Ang-(1-7)-Mas axis can be considered a possible therapeutic target for treating patients with muscular disorders.

Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

Directory of Open Access Journals (Sweden)

Ronaldo Altenburg Gismondi

2015-01-01

Full Text Available AbstractBackground:Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness.Objective:To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness.Methods:Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring, endothelial function (brachial artery flow-mediated dilation, and vascular stiffness (pulse wave velocity were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively.Results:The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007, and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003 when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820. There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586.Conclusion:Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Body fluids, circadian blood pressure and plasma renin during growth hormone administration: a placebo-controlled study with two growth hormone doses in healthy adults

DEFF Research Database (Denmark)

Møller, Jens; Jørgensen, Jens Otto Lunde; Frandsen, Erik

1995-01-01

Abstract Side effects that can be related to fluid retention are common during the initial phases of growth hormone (GH) administration. The aim of this study was to examine the changes in body fluid compartments, diurnal blood pressure and plasma renin concentration during GH administration......-2, 20.65 +/- 0.94; pbody water (l) increased significantly during GH administration (placebo, 50.8 +/- 2.6; 3 IU m-2, 52.6 +/- 2.3; 6 IU m-2, 53.9 +/- 1.8, p... of treatment a significant increase in renin (p = 0.03) was observed. Mean diurnal blood pressure levels remained unchanged, whereas mean diurnal heart rate (min-1) increased significantly (placebo, 75 +/- 3.6; 3 IU m-2, 79 +/- 3.2; 6 IU m-2, 79 +/- 3.7; p

Expression and effect of inhibition of aminopeptidase-A during nephrogenesis.

NARCIS (Netherlands)

Dijkman, H.B.P.M.; Assmann, K.J.M.; Steenbergen, E.; Wetzels, J.F.M.

2006-01-01

Aminopeptidase-A (APA) is a metalloprotease that cleaves N-terminal aspartyl and glutamyl residues from peptides. Its best-known substrate is angiotensin II (Ang II), the most active compound of the renin-angiotensin system (RAS). The RAS is involved in renal development. Most components of the RAS

Substrate effects on terahertz metamaterial resonances for various metal thicknesses

International Nuclear Information System (INIS)

Park, S. J.; Ahn, Y. H.

2014-01-01

We demonstrate dielectric substrate effects on the resonance shift of terahertz metamaterials with various metal thicknesses by using finite-difference time-domain simulations. We found a small red shift in the metamaterial resonance with increasing metal thickness for the free-standing case. Conversely, when the metamaterial pattern was supported by a substrate with a high dielectric constant, the resonant frequency exhibited a large blue shift because the relative contribution of the substrate's refractive index to the resonant frequency decreased drastically as we increased the metal thickness. We determined the substrate's refractive index, 1.26, at which the metamaterial resonance was independent of the metal thickness. We extracted the effective refractive index as a function of the substrate's refractive index explicitly, which was noticeably different for different film thicknesses.

The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

Science.gov (United States)

Vaidya, A; Brown, J M; Williams, J S

2015-09-01

There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

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Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

2015-08-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes

DEFF Research Database (Denmark)

Schievink, B; Kröpelin, T; Mulder, S

2016-01-01

AIMS: To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD. METHODS: We used data from...

Effect of Substrate on Biogas Yield | Adamu | Global Journal of ...

African Journals Online (AJOL)

Biogas technology converts biological matter or biological waste (substrate) into energy and simultaneously helps to improve the quality of life and the environment. The effect of substrate on biogas yield was studied by using different substrate in laboratory scale experiment using water displacement method to monitor the ...

Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

DEFF Research Database (Denmark)

Heijnen, Bart Fj; Pelkmans, Leonie Pj; Danser, Ah Jan

2013-01-01

This study investigated renin-angiotensin system (RAS)-induced cardiac remodeling and its reversibility in the presence and absence of high blood pressure (BP) in Cyp1a1-Ren2 transgenic inducible hypertensive rats (IHR). In IHR (pro)renin levels and BP can be dose-dependently titrated by oral...... administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically...

Substrate deposit effect on the characteristic of an intertidal macroalgal community

Digital Repository Service at National Institute of Oceanography (India)

Imchen, T.

Present study consists the effect of substrate deposit (silt, clay, sand, gravel and shards of shells) on the characteristic of an intertidal rocky shore macroalgae Macroalgal assemblage was segregated from substrate deposit in two stages Substrate...

Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes.

Science.gov (United States)

Clase, Catherine M; Barzilay, Joshua; Gao, Peggy; Smyth, Andrew; Schmieder, Roland E; Tobe, Sheldon; Teo, Koon K; Yusuf, Salim; Mann, Johannes F E

2017-03-01

Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

The Effect of Substrate Topography on Coating Cathodic Delamination

DEFF Research Database (Denmark)

Erik Weinell, Claus; Sørensen, Per A.; Kiil, Søren

2011-01-01

This article describes the effect of steel substrate topography on coating cathodic delamination. The study showed that the surface preparation can be used to control and minimize the rate of cathodic delamination. The coating should have maximum wetting properties so that substrates with high...

[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

Science.gov (United States)

Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu

2015-07-01

Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, PCushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (PCushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

(Pro)renin receptor: Involvement in diabetic retinopathy and development of molecular targeted therapy.

Science.gov (United States)

Kanda, Atsuhiro; Ishida, Susumu

2018-03-25

The renin-angiotensin system (RAS), a crucial regulator of systemic blood pressure (circulatory RAS), plays distinct roles in pathological angiogenesis and inflammation in various organs (tissue RAS), such as diabetic microvascular complications. Using ocular clinical samples and animal disease models, we elucidated molecular mechanisms in which tissue RAS excites the expression of vascular endothelial growth factor (VEGF)-A responsible for retinal inflammation and angiogenesis, the two major pathological events in diabetic retinopathy (DR). Furthermore, we showed the involvement of (pro)renin receptor [(P)RR] in retinal RAS activation and its concurrent intracellular signal transduction (e.g., extracellular signal-regulated kinase); namely, the (P)RR-induced dual pathogenic bioactivity referred to as the receptor-associated prorenin system. Indeed, neovascular endothelial cells in the fibrovascular tissue collected from eyes with proliferative DR were immunoreactive for the receptor-associated prorenin system components including prorenin, (P)RR, phosphorylated extracellular signal-regulated kinase and VEGF-A. Protein levels of soluble (P)RR increased with its positive correlations with prorenin, renin enzymatic activity and VEGF in the vitreous of proliferative DR eyes, suggesting a close link between (P)RR and VEGF-A-driven angiogenic activity. Furthermore, we revealed an unsuspected, PAPS-independent role of (P)RR in glucose-induced oxidative stress. Recently, we developed an innovative single-strand ribonucleic acid interference molecule selectively targeting human and mouse (P)RR, and confirmed its efficacy in suppressing diabetes-induced retinal inflammation in mice. Our data using clinical samples and animal models suggested the significant implication of (P)RR in the pathogenesis of DR, and the potential usefulness of the ribonucleic acid interference molecule as a therapeutic agent to attenuate ocular inflammation and angiogenesis. © 2018 The Authors

Dietary Sodium Suppresses Digestive Efficiency via the Renin-Angiotensin System.

Science.gov (United States)

Weidemann, Benjamin J; Voong, Susan; Morales-Santiago, Fabiola I; Kahn, Michael Z; Ni, Jonathan; Littlejohn, Nicole K; Claflin, Kristin E; Burnett, Colin M L; Pearson, Nicole A; Lutter, Michael L; Grobe, Justin L

2015-06-11

Dietary fats and sodium are both palatable and are hypothesized to synergistically contribute to ingestive behavior and thereby obesity. Contrary to this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary sodium content. This suppressive effect of dietary sodium upon weight gain was mediated specifically through a reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement of circulating angiotensin II levels reversed the effects of high dietary sodium to suppress digestive efficiency. While the AT1 receptor antagonist losartan had no effect in mice fed low sodium, the AT2 receptor antagonist PD-123,319 suppressed digestive efficiency. Correspondingly, genetic deletion of the AT2 receptor in FVB/NCrl mice resulted in suppressed digestive efficiency even on a standard chow diet. Together these data underscore the importance of digestive efficiency in the pathogenesis of obesity, and implicate dietary sodium, the renin-angiotensin system, and the AT2 receptor in the control of digestive efficiency regardless of mouse strain or macronutrient composition of the diet. These findings highlight the need for greater understanding of nutrient absorption control physiology, and prompt more uniform assessment of digestive efficiency in animal studies of energy balance.

Potential of a renin inhibitory peptide from the red seaweed Palmaria palmata as a functional food ingredient following confirmation and characterization of a hypotensive effect in spontaneously hypertensive rats.

Science.gov (United States)

Fitzgerald, Ciaran; Aluko, Rotimi E; Hossain, Mohammad; Rai, Dilip K; Hayes, Maria

2014-08-20

This work examined the resistance of the renin inhibitory, tridecapeptide IRLIIVLMPILMA derived previously from a Palmaria palmata papain hydrolysate, during gastrointestinal (GI) transit. Following simulated GI digestion, breakdown products were identified using mass spectrometry analysis and the known renin and angiotensin I converting enzyme inhibitory dipeptide IR was identified. In vivo animal studies using spontaneously hypertensive rats (SHRs) were used to confirm the antihypertensive effects of both the tridecapeptide IRLIIVLMPILMA and the seaweed protein hydrolysate from which this peptide was isolated. After 24 h, the SHR group fed the P. palmata protein hydrolysate recorded a drop of 34 mm Hg in systolic blood pressure (SBP) from 187 (±0.25) to 153 (± 0.64) mm Hg SBP, while the group fed the tridecapeptide IRLIIVLMPLIMA presented a drop of 33 mm Hg in blood pressure from 187 (±0.95) to 154 (±0.94) mm Hg SBP compared to the SBP recorded at time zero. The results of this study indicate that the seaweed protein derived hydrolysate has potential for use as antihypertensive agents and that the tridecapeptide is cleaved and activated to the dipeptide IR when it travels through the GI tract. Both the hydrolysate and peptide reduced SHR blood pressure when administered orally over a 24 h period.

Neuronal nitric oxide synthase supports Renin release during sodium restriction through inhibition of phosphodiesterase 3

DEFF Research Database (Denmark)

Sällström, Johan; Jensen, Boye L; Skøtt, Ole

2010-01-01

NOS supports renin release by cyclic guanosine monophosphate (cGMP)-mediated inhibition of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase 3 (PDE3) in juxtaglomerular (JG) cells. METHODS: The experiments were performed in conscious nNOS⁻(/)⁻ and wild types after 10 days on a low-sodium diet...... by measurements of inulin- and para-amino hippuric acid (PAH) clearances, respectively. RESULTS: The basal PRC was reduced in nNOS⁻(/)⁻ compared to the wild types. Administration of milrinone caused a more pronounced PRC increase in nNOS⁻(/)⁻, resulting in normalized renin levels, whereas PDE5 inhibition did...... not affect PRC in any genotype. The blood pressure was similar in both genotypes, and milrinone did not affect blood pressure compared to vehicle. GFR and RPF were similar at baseline and were reduced by milrinone. CONCLUSIONS: The present study provides in vivo evidence supporting the view that NO...

Magnus-induced ratchet effects for skyrmions interacting with asymmetric substrates

Science.gov (United States)

Reichhardt, C.; Ray, D.; Olson Reichhardt, C. J.

2015-07-01

We show using numerical simulations that pronounced ratchet effects can occur for ac driven skyrmions moving over asymmetric quasi-one-dimensional substrates. We find a new type of ratchet effect called a Magnus-induced transverse ratchet that arises when the ac driving force is applied perpendicular rather than parallel to the asymmetry direction of the substrate. This transverse ratchet effect only occurs when the Magnus term is finite, and the threshold ac amplitude needed to induce it decreases as the Magnus term becomes more prominent. Ratcheting skyrmions follow ordered orbits in which the net displacement parallel to the substrate asymmetry direction is quantized. Skyrmion ratchets represent a new ac current-based method for controlling skyrmion positions and motion for spintronic applications.

The effect of clay amendment on substrate properties and growth of woody plants

Directory of Open Access Journals (Sweden)

Tomáš Meisl

2012-01-01

Full Text Available This work deals with the effect of two clay products differing in particle size distribution on properties of growing substrate and on growth of containerized woody plants in substrates amended with these clay products. Fine and coarse clay were added to a peat substrate, each at two rates. The peat substrate without clay was used as a control. The substrates were tested in experiments with two woody ornamentals (Thuja occidentalis ’Smaragd’ and Prunus cistena. Chemical and physical properties of the substrates were measured according to European Standards before planting. Proportion of water categories differing in availability to the plants were calculated from retention curves measured on the sand box. Properties of substrates in containers with and without plants were evaluated in the same way at the end of the culture. Clay addition changed chemical and physical properties of the tested substrates in terms: available nutrients content, particle density, bulk density, total pore volume, easy available water, water buffering capacity, air capacity, and shrinkage. The effect of fine clay was much stronger. In comparison with the clear effect of clay addition on the substrate chemical and physical properties, the effect on the growth and quality of model woody plants was not so explicit.

Determinants of the renin-angiotensin-aldosterone system in cirrhosis with special emphasis on the central blood volume

DEFF Research Database (Denmark)

Møller, Søren; Bendtsen, Flemming; Henriksen, Jens H

2006-01-01

OBJECTIVE: Several studies have shown activation of the renin-angiotensin-aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have several determinants, the system is often considered a surrogate marker of effective hypovolaemia. In this study we investigated the activity...... of the RAAS and its potential determinants with special focus on the central and arterial blood volume (CBV). MATERIAL AND METHODS: Eighty-nine patients (Child class A/B/C: 19/41/29) and 32 controls were included in the study. All were given a haemodynamic examination with measurement of determinants...

New Frontiers in the Intrarenal Renin-Angiotensin System: A Critical Review of Classical and New Paradigms

Science.gov (United States)

Zhuo, Jia L.; Ferrao, Fernanda M.; Zheng, Yun; Li, Xiao C.

2013-01-01

The renin-angiotensin system (RAS) is well-recognized as one of the oldest and most important regulators of arterial blood pressure, cardiovascular, and renal function. New frontiers have recently emerged in the RAS research well beyond its classic paradigm as a potent vasoconstrictor, an aldosterone release stimulator, or a sodium-retaining hormone. First, two new members of the RAS have been uncovered, which include the renin/(Pro)renin receptor (PRR) and angiotensin-converting enzyme 2 (ACE2). Recent studies suggest that prorenin may act on the PRR independent of the classical ACE/ANG II/AT1 receptor axis, whereas ACE2 may degrade ANG II to generate ANG (1–7), which activates the Mas receptor. Second, there is increasing evidence that ANG II may function as an intracellular peptide to activate intracellular and/or nuclear receptors. Third, currently there is a debate on the relative contribution of systemic versus intrarenal RAS to the physiological regulation of blood pressure and the development of hypertension. The objectives of this article are to review and discuss the new insights and perspectives derived from recent studies using novel transgenic mice that either overexpress or are deficient of one key enzyme, ANG peptide, or receptor of the RAS. This information may help us better understand how ANG II acts, both independently or through interactions with other members of the system, to regulate the kidney function and blood pressure in health and disease. PMID:24273531

The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

Energy Technology Data Exchange (ETDEWEB)

Kim, Suyeon [University of Tennessee, Knoxville (UTK); Soltani-Bejnood, Morvarid [University of Tennessee, Knoxville (UTK); Quignard-Boulange, Annie [Centre Biomedical des Cordeliers, Paris, France; Massiera, Florence [Centre de Biochimie, Nice, France; Teboul, Michele [Centre de Biochimie, Nice, France; Ailhaud, Gerard [Centre de Biochimie, Nice, France; Kim, Jung [University of Tennessee, Knoxville (UTK); Moustaid-Moussa, Naima [University of Tennessee, Knoxville (UTK); Voy, Brynn H [ORNL

2006-07-01

BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO), and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

Effect Of Various Substrates On Eudrilus eugeniae (Oligochaeta Production

Directory of Open Access Journals (Sweden)

Mpoame, M.

1994-01-01

Full Text Available In order to assess the effects of substrate on Eudrilus eugeniae production, 360 worms were raised in plastic buckets containing manure either from cattle (BV, from sheep (CM, from rabbit (CL, and from chicken (FP. At the end of the experiment which lasted 4 months, worm productivity was estimated at 111.9 g/kg of substrate in CL, 86.3 g/kg in CM, and 33.0 g/kg in BV. Substrate FP was inadequate as worms escaped from it. In another trial aiming at determining some of E. Eugeniae's reproductive parameters, each of the 3 substrates BV, CL, and CM was distributed into 15 plastic half bottles and was inoculated with one cocoon. In the 3 substrates cocoon incubation time and growing period were estimated at 3 to 4 weeks and 6 to 7 weeks respectively. Cocoons were laid approximately a week after the pairing of worms. On the average, each worm laid 2 cocoons per week.

Stress in film/substrate system due to diffusion and thermal misfit effects

International Nuclear Information System (INIS)

Shao Shanshan; Xuan Fuzhen; Wang Zhengdong; Tu Shantung

2009-01-01

The stress in film/substrate systems has been analysed taking into consideration the coupling effects of diffusion and thermal misfit within the framework of Fick's second law. The solution of diffusion-induced stress in a film/substrate system involving the thermal misfit stress feedback is developed. The effects of modulus ratios, diffusivity ratios, thickness ratios of the substrate and the film and the partial molar volume of the diffusing component on the stress distribution in the film/substrate system are then discussed with the help of the finite difference method. Results indicate that the stresses in the film/substrate system vary with diffusion time. Diffusion enhances the magnitudes of film stress when the thermal misfit stress is compressive in the film. Furthermore, the absolute values of stress in the film increase with the increasing modulus ratios of the substrate and film, while they reduce with the increasing partial molar volume of the diffusing component and the diffusivity ratio of the substrate and the film.

Dexamethasone-responsive hypertension in young women with suppressed renin and aldosterone

International Nuclear Information System (INIS)

Hoefnagels, W.H.L.; Hofman, J.A.; Smals, A.G.H.; Drayer, J.I.M.; Kloppenborg, P.W.C.; Benraad, T.J.

1978-01-01

Pronounced hypoaldosteronism was found in three young women with hypertension and symptoms of mineralocorticoid overproduction - i.e., hyporeninaemia, hypokalaemia, and a fall in blood-pressure after diuretic therapy. Plasma 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone concentrations were normal. Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion. The data suggest that hypertension in these patients is maintained by overproduction of an unknown adrenocorticotropin-dependent mineralocortocoid. (author)

Role of proteinuria in the regulation of renal renin-angiotensin system components in unilateral proteinuric rats

NARCIS (Netherlands)

Deelman, LE; Navis, G; Wietses, M; de Zeeuw, D; Henning, RH

Renin-angiotensin system (RAS) overactivity has been implied in progressive renal function loss. We investigated whether changes in the renal expression of RAS components are specifically associated with the proteinuric kidney. Unilateral adriamycin-induced proteinuria was obtained by clamping the

Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

Science.gov (United States)

Sabharwal, Rasna; Chapleau, Mark W

2014-04-01

New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of

[Changes in the renin-angiotensin-aldosterone system and water-salt exchange in mining workers in coal mines].

Science.gov (United States)

Rebrov, B A

1996-01-01

Blood and urine content of electrolytes and creatinine was determined in 76 essentially healthy miners before and after work shift, as was activity of plasma renin, blood plasma level of aldosterone and its urinary excretion, with the aid of radioimmunoassay. The greatest activity of the renin-angiotensine-aldosterone system (RAAS) occurred in those individuals engaged in hard physical labour under most harsh conditions of underground workings, this being recordable not only is response to the load but also from the very start. Controls and miners doing jobs of medium-level strenuousness demonstrated changes in the correlations between RAAS and water-salt balance after the work shift as compared with those before the work shift, while in those miners engaged in hard work correlations RAAS-water-salt exchange remained practically the same throughout the study.

A high sodium intake reduces antiproteinuric response to renin-angiotensin-aldosterone system blockade in kidney transplant recipients.

Science.gov (United States)

Monfá, Elena; Rodrigo, Emilio; Belmar, Lara; Sango, Cristina; Moussa, Fozi; Ruiz San Millán, Juan Carlos; Piñera, Celestino; Fernández-Fresnedo, Gema; Arias, Manuel

Post-transplant proteinuria is associated with lower graft and patient survival. Renin-angiotensin-aldosterone system blockers are used to reduce proteinuria and improve renal outcome. Although it is known that a high salt intake blunts the antiproteinuric effect of ACEI and ARB drugs in non-transplant patients, this effect has not been studied in kidney transplant recipients. To analyse the relationship between sodium intake and the antiproteinuric effect of ACEI/ARB drugs in kidney transplant recipients. We selected 103 kidney transplant recipients receiving ACEI/ARB drugs for more than 6 months due to proteinuria>1 g/day. Proteinuria was analysed at baseline and at 6 months after starting ACEI/ARB treatment. Salt intake was estimated by urinary sodium to creatinine ratio (uNa/Cr). Proteinuria fell to less than 1g/day in 46 patients (44.7%). High uNa/Cr was associated with a smaller proteinuria decrease (r=-0.251, P=.011). The percentage proteinuria reduction was significantly lower in patients in the highest uNa/Cr tertile [63.9% (IQR 47.1%), 60.1% (IQR 55.4%), 38.9% (IQR 85.5%), P=.047]. High uNa/Cr independently relates (OR 2.406 per 100 mEq/g, 95% CI: 1.008-5.745, P=.048) to an antiproteinuric response <50% after renin-angiotensin-aldosterone system blockade. A high salt intake results in a smaller proteinuria decrease in kidney transplant recipients with proteinuria treated with ACEI/ARB drugs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Effects of substrate on piezoelectricity of electrospun poly(vinylidene fluoride)-nanofiber-based energy generators.

Science.gov (United States)

Lee, Byoung-Sun; Park, Boongik; Yang, Ho-Sung; Han, Jin Woo; Choong, Chweelin; Bae, Jihyun; Lee, Kihwan; Yu, Woong-Ryeol; Jeong, Unyong; Chung, U-In; Park, Jong-Jin; Kim, Ohyun

2014-03-12

We report the effects of various substrates and substrate thicknesses on electrospun poly(vinylidene fluoride) (PVDF)-nanofiber-based energy harvesters. The electrospun PVDF nanofibers showed an average diameter of 84.6 ± 23.5 nm. A high relative β-phase fraction (85.2%) was achieved by applying high voltage during electrospinning. The prepared PVDF nanofibers thus generated considerable piezoelectric potential in accordance with the sound-driven mechanical vibrations of the substrates. Slide glass, poly(ethylene terephthalate), poly(ethylene naphthalate), and paper substrates were used to investigate the effects of the intrinsic and extrinsic substrate properties on the piezoelectricity of the energy harvesters. The thinnest paper substrate (66 μm) with a moderate Young's modulus showed the highest voltage output (0.4885 V). We used high-performance 76, 66, and 33 μm thick papers to determine the effect of paper thickness on the output voltage. The thinnest paper substrate resulted in the highest voltage output (0.7781 V), and the numerical analyses of the sound-driven mechanical deformation strongly support the hypothesis that substrate thickness has a considerable effect on piezoelectric performance.

Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups

Science.gov (United States)

Ortiz, R. M.; Wade, C. E.; Ortiz, C. L.

2000-01-01

The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period. Copyright 2000 Academic Press.

Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model

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Yuki Narita

2016-02-01

Full Text Available We previously reported that camostat mesilate (CM had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE, a renin-angiotensin-aldosterone system (RAS inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day and/or TE (10 mg/kg/day on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA and plasma aldosterone concentration (PAC was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.

Renin-angiotensin system antagonists, glomerular filtration rate and blood pressure

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D.D. Ivanov

2018-02-01

Full Text Available The article deals with the mModern data on the influence of renin-angiotensin system blockers on the glomerular filtration rate, the level of arterial pressure and the outcome of chronic kidney disease. The strategy of  rennin-angiotensine blockade is offered to be changed depending on the criteria va­lues of glomerular filtration rate: a combination of inhibitors of angiotensin-converting enzyme + angiotensin receptors blo­ckers, monotherapy and drug withdrawal in glomerular filtration rate under 15–30 ml/min/m2. The formula BRIMONEL for treatment of chronic kidney disease is given.

Calcium and osmotic stimulation in renin release from isolated rat glomeruli

DEFF Research Database (Denmark)

Skøtt, O

1986-01-01

of the RR rate preceding the stimulus. Removal of calcium stimulated the RR by 10 times (n = 5, p less than 0.001) and a subsequent decrease in osmolality of 20 mOsm/kg stimulated the RR proportionally to that observed in the series containing 2 mM calcium. A decrease in osmolality was able to stimulate RR......The effects of changes in osmolality and calcium concentration on renin release (RR) from isolated superfused rat glomeruli were studied. The undisturbed RR followed a first order fall with a half-time of about 100 min (n = 45). Changes in the osmolality between 270 and 350 mOsm/kg resulted in dose......-dependent changes in the RR rates. Hypoosmotic treatment stimulated the RR transiently, whereas hyperosmotic treatment produced a sustained inhibition. The dose-response relationship was log-linear between 270 and 320 mOsm/kg. A decrease in osmolality of 20 mOsm/kg gave proportional increases in RR irrespectively...

Regulation of the renin-angiotensin-aldosterone system in fibromyalgia.

Science.gov (United States)

Maliszewski, Anne M; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K

2002-07-01

To assess the function of the renin-angiotensin-aldosterone (RAA) system in women with fibromyalgia (FM) compared to healthy women. Women with FM [n = 14, age 41.0+/-7.2 yrs, body mass index (BMI) 26.4+/-5.4 kg/m2] and healthy women (n = 13, age 40.0+/-7.7 yrs, BMI 25.0+/-5.0 kg/m2) were placed on a low sodium diet (10 mEq sodium/day) for 5 days. After being supine and fasting overnight, subjects received an intravenous infusion of angiotensin II at successive doses of 1, 3, and 10 ng/kg/min for 45 min per dose. Blood pressure (BP), plasma renin activity (PRA), aldosterone, and cortisol were measured at baseline and after each dose of angiotensin II. Prior to sodium restriction, women with FM completed the Hopkins Symptom Checklist-90, which included a question grading the extent of dizziness/faintness on a scale of 0 (none) to 4 (extremely). After dietary sodium restriction, baseline PRA, aldosterone, and supine BP were similar in healthy women and women with FM. Aldosterone and BP rose in response to infused angiotensin II; these responses did not differ significantly between healthy women and women with FM. In women with FM, symptoms of dizziness correlated inversely with BMI (r = -0.81, p < 0.001) and the systolic BP response to 10 ng/kg/min angiotensin II (r = -0.81, p < 0.001). The functioning of the RAA system, including the vascular response to angiotensin II, was intact in women with FM compared to healthy women. However, women with FM who complained of dizziness had a blunted vascular response to angiotensin II. This blunted vascular response may indicate intravascular volume depletion in women with symptoms of dizziness.

Graz Endocrine Causes of Hypertension (GECOH study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism

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Dobnig Harald

2009-04-01

Full Text Available Abstract Background Primary aldosteronism (PA affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH study we aim to prospectively evaluate diagnostic procedures for PA. Methods and design In this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin. Conclusion Screening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.

Synergistic effects of semiconductor substrate and noble metal nano-particles on SERS effect both theoretical and experimental aspects

Science.gov (United States)

Yang, Chen; Liang, Pei; Tang, Lisha; Zhou, Yongfeng; Cao, Yanting; Wu, Yanxiong; Zhang, De; Dong, Qianmin; Huang, Jie; He, Peng

2018-04-01

As a means of chemical identification and analysis, Surface enhanced Raman spectroscopy (SERS), with the advantages of high sensitivity and selectivity, non-destructive, high repeatability and in situ detection etc., has important significance in the field of composition detection, environmental science, biological medicine etc. Physical model of coupling effect between different semiconductor substrates and noble metal particles were investigated by using 3D-FDTD method. Mechanism and the effects of excitation wavelength, particle spacing and semiconductor substrate types on the SERS effect were discussed. The results showed that the optimal excitation wavelengths of three noble metals of Ag, Au, Cu, were located at 510, 600 and 630 nm, respectively; SERS effect of Ag, Au, Cu increases with the decreasing of the inter distance of particles, while the distance of the NPs reaches the critical value of 3 nm, the strength of SERS effect will be greatly enhanced. For the four different types of substrate of Ge, Si, SiO2 (glass) and Al2O3, the SERS effect of Ag on SiO2 > Ge > Al2O3 > Si. For Au and Cu nanoparticles, the SERS effect of them on oxide substrate is stronger than that on non-oxide substrate. In order to verify FDTD simulations, taking silver nanoparticles as an example, and silver nanoparticles prepared by chemical method were spinning coating on the four different substrates with R6G as probe molecules. The results show that the experimental results are consistent with FDTD theoretical simulations, and the SERS enhancement effect of Ag-SiO2 substrate is best. The results of this study have important theoretical significance to explain the variations of SERS enhancement on different noble metals, which is also an important guide for the preparation of SERS substrates, especially for the microfluidics. The better Raman effect can be realized by choosing proper substrate type, particle spacing and excitation wavelength, result in expanding the depth and width

Blockade of AT1 receptors by losartan did not affect renin gene expression in kidney medulla

Czech Academy of Sciences Publication Activity Database

Tybitanclová, K.; Szabová, L.; Grima, M.; Ingert, C.; Železná, Blanka; Zórad, Š.

2006-01-01

Roč. 25, č. 1 (2006), s. 43-51 ISSN 0231-5882 Grant - others:VEGA(SK) 2/5090/25 Institutional research plan: CEZ:AV0Z50520514 Keywords : AT1 receptor * renin-angiotensin system * kidneys Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.771, year: 2006

Salt sensitivity of renin secretion, glomerular filtration rate and blood pressure in conscious Sprague-Dawley rats

DEFF Research Database (Denmark)

Isaksson, G L; Stubbe, J; Hansen, Per Lyngs

2014-01-01

We hypothesized that in normal rats in metabolic steady state, (i) the plasma renin concentration (PRC) is log-linearly related to Na(+) intake (NaI), (ii) the concurrent changes in mean arterial pressure (MABP) and glomerular filtration rate (GFR) are negligible and (iii) the function PRC...

Control of renin secretion from rat juxtaglomerular cells by cAMP-specific phosphodiesterases

DEFF Research Database (Denmark)

Friis, Ulla G; Jensen, Boye L; Sethi, Shala

2002-01-01

, and the PDE4 inhibitor rolipram enhanced cellular cAMP content. Dialysis of single JG cells with cAMP in whole-cell patch-clamp experiments led to concentration-dependent, biphasic changes in cell membrane capacitance (C(m)) with a marked increase in C(m) at 1 micromol/L, no net change at 10 micromol....../L, and a decrease at 100 micromol/L cAMP. cGMP also had a dual effect on C(m) at 10-fold higher concentration compared with cAMP. Trequinsin, milrinone, and rolipram mimicked the effect of cAMP on C(m). Trequinsin, cAMP, and cGMP enhanced outward current 2- to 3-fold at positive membrane potentials. The effects...... of cAMP, cGMP, and trequinsin on C(m) and cell currents were abolished by inhibition of protein kinase A with Rp-cAMPs. We conclude that degradation of cAMP by PDE3 and PDE4 contributes to regulation of renin release from JG cells. Our data provide evidence at the cellular level that stimulation...

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension.

Science.gov (United States)

Shim, Kwang Yong; Eom, Young Woo; Kim, Moon Young; Kang, Seong Hee; Baik, Soon Koo

2018-05-01

The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study

DEFF Research Database (Denmark)

Krum, Henry; Massie, Barry; Abraham, William T

2011-01-01

AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs......S for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma...... levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril...

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

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Jose L. Labandeira-Garcia

2017-05-01

Full Text Available Microglia can transform into proinflammatory/classically activated (M1 or anti-inflammatory/alternatively activated (M2 phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory to M2 (immunoregulatory phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS on microglial polarization are less known. It is well known that there is a “classical” circulating RAS; however, a second RAS (local or tissue RAS has been observed in many tissues, including brain. The locally formed angiotensin is involved in local pathological changes of these tissues and modulates immune cells, which are equipped with all the components of the RAS. There are also recent data showing that brain RAS plays a major role in microglial polarization. Level of microglial NADPH-oxidase (Nox activation is a major regulator of the shift between M1/proinflammatory and M2/immunoregulatory microglial phenotypes so that Nox activation promotes the proinflammatory and inhibits the immunoregulatory phenotype. Angiotensin II (Ang II, via its type 1 receptor (AT1, is a major activator of the NADPH-oxidase complex, leading to pro-oxidative and pro-inflammatory effects. However, these effects are counteracted by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and Angiotensin 1–7/Mas receptor (MasR signaling. In addition, activation of prorenin-renin receptors may contribute to activation of the proinflammatory phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2 receptor expression, which may contribute to a pro-oxidative pro-inflammatory state and the increase in neuron vulnerability. Several recent studies have shown interactions between the brain RAS and different factors involved in microglial polarization

Combination inhibition of the renin-angiotensin system: is more better?

Science.gov (United States)

Krause, Michelle W; Fonseca, Vivian A; Shah, Sudhir V

2011-08-01

Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are considered the standard of care for treatment of cardiovascular disease and chronic kidney disease. Combination therapy with both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers effectively inhibits the renin-angiotensin system as well as potentiates the vasodilatory effects of bradykinin. It has been advocated that this dual blockade approach theoretically should result in improved clinical outcomes in both cardiovascular disease and chronic kidney disease. Clinical trial evidence for the use of combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in cardiovascular disease has provided conflicting results in hypertension, congestive heart failure, and ischemic heart disease. Clinical trial evidence to support combination therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chronic kidney disease has largely been based on proteinuria reduction as a surrogate marker for clinically meaningful outcomes. Recent large-scale randomized clinical trials have not been able to validate protection in halting progression in chronic kidney disease with a dual blockade approach. This review serves as an appraisal on the clinical evidence of combination angiotensin-converting enzyme inhibition and angiotensin II receptor blockade in both cardiovascular disease and chronic kidney disease.

Role of the renin-angiotensin system, renal sympathetic nerve system, and oxidative stress in chronic foot shock-induced hypertension in rats.

Science.gov (United States)

Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

2015-01-01

The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension.

The role of vascular protein and renin in chronic two-kidney, one clip Goldblatt hypertension

International Nuclear Information System (INIS)

Nakada, T.; Yamori, Y.

1982-01-01

Chronic hypertension was induced in rats by application of a clip for 17 or 20 weeks to the unilateral renal artery and leaving the contrarenal vessel intact. Some of the rats received antihypertensive treatment with phenoxybenzamine (POB). 3 H-proline was injected into all rats in the 17th experimental week to observe the in vivo incorporation rates of 3 H-proline into vascular non-collagenous protein and vascular collagen. Plasma renin activity (PRA) of decapitated rats was assayed in the terminal stage of the experiment. Significant differences were noted between 2K-1C hypertensive rats and sham-operated normotensive rats, the former rats having significantly higher incorporation rates of 3 H-proline into non-collagenous protein and collagen of testicular or mesenteric artery. These results indicate that increased synthesis of vascular non-collagenous protein as well as collagen, especially of small arteries, plays a major role for the pathogenesis of chronic hypertension in 2K-1C rats, and renin does not contribute to elevation of the blood pressure in the maintenance phase of this type of experimental hypertension

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

Science.gov (United States)

Graudal, Niels Albert; Hubeck-Graudal, Thorbjorn; Jurgens, Gesche

2017-04-09

In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved. To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to March 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the reference lists of relevant articles. Studies randomising persons to low-sodium and high-sodium diets were included if they evaluated at least one of the above outcome parameters. Two review authors independently collected data, which were analysed with Review Manager 5.3. A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level).The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP: mean difference (MD) -1.09 mmHg (95% confidence interval (CI): -1.63 to -0.56; P = 0.0001); 89 studies, 8569 participants; DBP: + 0.03 mmHg (MD 95% CI: -0.37 to 0.43; P = 0.89); 90 studies, 8833 participants. High-quality evidence. Black people with normotension: SBP: MD -4.02 mmHg (95% CI:-7.37 to -0.68; P = 0.002); seven studies, 506 participants; DBP: MD -2.01 mmHg (95% CI:-4.37 to 0.35; P = 0.09); seven studies, 506 participants. Moderate-quality evidence. Asian people with normotension: SBP: MD -0.72 mmHg (95% CI: -3.86 to 2.41; P = 0.65); DBP: MD -1.63 mmHg (95% CI:-3.35 to 0

Investigation the effects of metallic substrate surfaces due to ion-plasma treatment

International Nuclear Information System (INIS)

Shulaev, V.M.; Taran, V.S.; Timoshenko, A.I.; Gasilin, V.V.

2011-01-01

It has been found correlation between modification effects and duration of ion-plasma cleaning the substrate surface with titanium ions. Experiments were carried out using serial vacuum-arc equipment ''Bulat-6'' at the stationary mode in non-filtered titanium plasma, which contained considerable quantity of evaporated material droplets. The polished cylinder substrates (diameter and height 9,14,20 mm) have been treated. The substrates were manufactured of stainless steel 12X18H10T and non-oxygen copper M00b. The substrates surface roughness after ion-plasma treatment has been investigated with electron microscope JEOL JSM-840 and optic interference non-contact profilograph- profilometer ''Micron-alpha''. According obtained results the surface of copper and stainless steel substrates has been treated to intensive modification, i.e. substrate surface after treatment significantly differs from initial one. During final ion-plasma treatment a number of effects occur: purification from surface oxides is accompanied with metallic surface ''contamination'' by the cathode material macrodroplets, surface micromelting accompanied by roughness increase, the surface layer annealing with noticeable decrease of hardness.

Between-patient differences in the renal response to renin-angiotensin system intervention : clue to optimising renoprotective therapy?

NARCIS (Netherlands)

Laverman, GD; de Zeeuw, D; Navis, G

2002-01-01

Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II (Ang II), AT(1)-receptor blockers (ARB) is the cornerstone of renoprotective therapy. Still, the number of patients with end-stage renal disease is increasing worldwide,

Characterization of Antennas on Dielectric and Magnetic Substrates Effective Medium Approximation

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A. Sharaiha

2009-12-01

Full Text Available This paper presents a study of the effective medium approximation of a monopole antenna printed on either a dielectric or a magnetic substrate. Simple analytical formulas to determine the effective permeability of such an antenna have been proposed and validated. For this type of antenna as μr increases, the effective permeability will reach the value of 2 (maximum whereas, with the dielectric substrate, the effective permittivity continues to rise when increasing εr. This shows that, for very high permeability values, we will always have a size reduction below 30%.

Effect of the Substrate on Phonon Properties of Graphene Estimated by Raman Spectroscopy

Science.gov (United States)

Tivanov, M. S.; Kolesov, E. A.; Korolik, O. V.; Saad, A. M.; Komissarov, I. V.

2018-01-01

Low-temperature Raman studies of supported graphene are presented. A linear temperature dependence of 2D peak linewidths was observed with the coefficients of 0.036 and 0.033 cm^{-1}/K for graphene on copper and glass substrates, respectively, while G peak linewidths remained unchanged throughout the whole temperature range. The different values observed for graphene on glass and copper substrates were explained in terms of the substrate effect on phonon-phonon and electron-phonon interaction properties of the material. The results of the present study can be used to consider substrate effects on phonon transport in graphene for nanoelectronic device engineering.

The PGE(2)-EP4 receptor is necessary for stimulation of the renin-angiotensin-aldosterone system in response to low dietary salt intake in vivo

DEFF Research Database (Denmark)

Pöschke, Antje; Kern, Niklas; Maruyama, Takayuki

2012-01-01

, creatinine clearance, and plasma antidiuretic hormone (ADH) concentration. Following salt restriction, plasma renin and aldosterone concentrations and kidney renin mRNA level rose significantly in EP4(+/+) but not in EP4(-/-) and in wild-type mice treated with EP4 antagonist ONO-AE3-208. In the latter two...... groups, the low-salt diet caused a significantly greater rise in PGE(2) excretion. Furthermore, mRNA expression for COX-2 and PGE(2) synthetic activity was significantly greater in EP4(-/-) than in EP4(+/+) mice. We conclude that low dietary salt intake induces expression of COX-2 followed by enhanced...... renal PGE(2) synthesis, which stimulates the renin-angiotensin-aldosterone system by activation of EP4 receptor. Most likely, defects at the step of EP4 receptor block negative feedback mechanisms on the renal COX system, leading to persistently high PGE(2) levels, diuresis, and K(+) loss....

Neuronal nitric oxide synthase-deficient mice have impaired Renin release but normal blood pressure

DEFF Research Database (Denmark)

Sällström, Johan; Carlström, Mattias; Jensen, Boye L

2008-01-01

BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodiu......-116; doi:10.1038/ajh.2007.16American Journal of Hypertension (2008) 21 111-116; doi:10.1038/ajh.2007.16....

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

OpenAIRE

KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

1997-01-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was onl...

The effect of renin-angiotensin system blockade on renal protection in chronic kidney disease patients with hyperkalemia.

Science.gov (United States)

Lee, Ju-Hyun; Kwon, Young Eun; Park, Jung Tak; Lee, Mi Jung; Oh, Hyung Jung; Han, Seung Hyeok; Kang, Shin-Wook; Choi, Kyu Hun; Yoo, Tae-Hyun

2014-12-01

The aim of this study was to determine the effects of renin-angiotensin system (RAS) blockade maintenance on renal protection in chronic kidney disease (CKD) patients with hyperkalemia occurring during treatment with RAS blockade. CKD III or IV patients, who were prescribed with RAS blockers and also had hyperkalemia, were included. The study population was divided into two groups based on maintenance or withdrawal of RAS blocker. Renal outcomes (doubling of creatinine or end-stage renal disease) and incidence of hyperkalemia were compared between the two groups. Out of 258 subjects who developed hyperkalemia during treatment with RAS blockers, 150 (58.1%) patients continued on RAS blockades, while RAS blockades were discontinued for more than 3 months in the remaining 108 patients. Renal event-free survival was significantly higher in the maintenance group compared with the withdrawal group. Cox proportional hazard ratio for renal outcomes was 1.35 (95% CI: 1.08-1.92, p=0.04) in the withdrawal group compared with the maintenance group. However, the incidence of hyperkalemia and hyperkalemia-related hospitalization or mortality did not differ between the two groups. This study demonstrated that the maintenance of RAS blockade is beneficial for the preservation of renal function and relatively tolerable in patients with CKD and hyperkalemia occurring during treatment with RAS blockade. © The Author(s) 2014.

Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury.

Science.gov (United States)

Cao, Wei; Li, Aiqing; Li, Jiawen; Wu, Chunyi; Cui, Shuang; Zhou, Zhanmei; Liu, Youhua; Wilcox, Christopher S; Hou, Fan Fan

2017-09-01

A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p renal damage and dysfunction persisted after controlling blood pressure with hydralazine. This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.

Tea waste: an effective and economic substrate for oyster mushroom cultivation.

Science.gov (United States)

Yang, Doudou; Liang, Jin; Wang, Yunsheng; Sun, Feng; Tao, Hong; Xu, Qiang; Zhang, Liang; Zhang, Zhengzhu; Ho, Chi-Tang; Wan, Xiaochun

2016-01-30

Tea waste is the residue that remains after tea leaves have been extracted by hot water to obtain water-soluble components. The waste contains a re-usable energy substrate and nutrients which may pollute the environment if they are not dealt with appropriately. Other agricultural wastes have been widely studied as substrates for cultivating mushrooms. In the present study, we cultivated oyster mushroom using tea waste as substrate. To study the feasibility of re-using it, tea waste was added to the substrate at different ratios in different experimental groups. Three mushroom strains (39, 71 and YOU) were compared and evaluated. Mycelia growth rate, yield, biological efficiency and growth duration were measured. Substrates with different tea waste ratios showed different growth and yield performance. The substrate containing 40-60% of tea waste resulted in the highest yield. Tea waste could be used as an effective and economic substrate for oyster mushroom cultivation. This study also provided a useful way of dealing with massive amounts of tea waste. © 2015 Society of Chemical Industry.

Effect of substrate surface on electromigration-induced sliding at hetero-interfaces

International Nuclear Information System (INIS)

Kumar, Praveen; Dutta, Indranath

2013-01-01

Electromigration (EM)-induced interfacial sliding between a metal film and Si substrate occurs when (i) only few grains exist across the width of the film and (ii) diffusivity through the interfacial region is significantly greater than diffusivity through the film. Here, the effect of the substrate surface layer on the kinetics of EM-induced interfacial sliding is assessed using Si substrates coated with various thin film interlayers. The kinetics of interfacial sliding, and therefore the EM-driven mass flow rate, strongly depends on the type of the interlayer (and hence the substrate surface composition), such that strongly bonded interfaces with slower interfacial diffusivity produce slower sliding. (paper)

The renin-angiotensin system and aging in the kidney.

Science.gov (United States)

Yoon, Hye Eun; Choi, Bum Soon

2014-05-01

Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and functional changes in the aging kidney and age-related renal injury, and describes the underlying mechanisms of RAS-related renal aging. An improved understanding of the renal aging process may lead to better individualized care of the elderly and improved renal survival in age-related diseases.

(Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and Fibrosis.

Science.gov (United States)

Li, Zhen; Zhou, Lili; Wang, Yongping; Miao, Jinhua; Hong, Xue; Hou, Fan Fan; Liu, Youhua

2017-08-01

The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/ β -catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β -catenin induced PRR mRNA and protein expression in vitro Notably, forced expression of PRR potentiated Wnt1-mediated β -catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α -smooth muscle actin ( α -SMA). Conversely, knockdown of PRR by siRNA abolished β -catenin activation. PRR potentiation of Wnt/ β -catenin signaling did not require renin, but required vacuolar H + ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β -catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/ β -catenin signaling. Copyright © 2017 by the American Society of Nephrology.

Priming effects in Haplic Luvisol after different substrate additions

Science.gov (United States)

Bogomolova, I.; Blagodatskaya, E.; Blagodatsky, S.; Kuzyakov, Y.

2009-04-01

Although soils contain considerable amounts of soil organic carbon (SOC), most of it is not easily available for microorganisms. Addition of various substrates to soil (for example, plant residues, root exudates) may affect SOC mineralization. The addition of mineral nutrients, especially N, may also affect C turnover and so change the mineralization rate of SOC. Such short-term changes in mineralization of organic substance of soil were termed as "priming-effects" (Bingemann et al., 1953). Priming effect leads to additional mineralization of SOC (van Elsas and van Overbeek, 1993). It has been shown that not only plant residues induce priming effects (Sauerbeck, 1966; Stemmer et al., 1999; Bell et al., 2003), but also easily available substrates such as sugars or amino acids, which are present in soil solutions and root exudates (Vasconcellos, 1994; Shen and Bartha, 1997; Hamer and Marschner, 2002). Since easily available substrates may not only accelerate SOC mineralization, but also may retard it, Kuzyakov et al. (2000) differentiated between positive and negative priming effects. It is not clear until now, how long priming effects persists in soil after substrate addition, and if they are induced every time when a substrate becomes available in soil. So, the aim of this study was to evaluate effects of glucose and plant residues on SOM decomposition, and influence of glucose on plant residues decomposition in soil. The experimental layout was designed as two factor experiment: 1) plant residues and 2) available substrate amendment. Maize shoot residues (50 mg added to 5 g soil) were 14C labeled (9•104 DPM per 5 g soil). Soil without of any plant residues served as a control for this treatment. Two levels of D (+) glucose as easily available substrates were added after three months of pre-incubation of soil samples with maize residues: 0.009 mg glucose C g-1 soil and 0.225 mg glucose C g-1 soil. The glucose was uniformly labelled with 14C (2.37•104 DPM per 5

Heart-specific overexpression of (pro)renin receptor induces atrial fibrillation in mice.

Science.gov (United States)

Lian, Hong; Wang, Xiaojian; Wang, Juan; Liu, Ning; Zhang, Li; Lu, Yingdong; Yang, Yanmin; Zhang, Lianfeng

2015-04-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, causing substantial cardiovascular morbidity and mortality. The renin-angiotensin system (RAS) has been shown to be involved in the pathophysiology of AF. The (pro)renin receptor [(p)RR] is the last identified member of RAS. However, the role of (p)RR in AF is still unknown. Circulating levels of (p)RR were determined using an immunosorbent assay in 22 patients with AF (paroxysmal or persistent) and 22 healthy individuals. The plasma levels of (p)RR increased 3.6-fold in AF patients (Patrial flutter since 2 months, then spontaneously converted to atrial fibrillation by 10 months. The atria of the transgenic mice demonstrated significant dilation and fibrosis, and exhibited a high incidence of sudden death. Additionally, the genes of SERCA and HCN4, which are involved in the electrophysiology of AF, were significantly down-regulated and up-regulated respectively in transgenic mice atria. The phosphorylation of Erk1/2 significantly increased in the atria of the transgenic mice, and the activated Erk1/2 was found predominantly in cardiac fibroblasts, suggesting that the transgenic (p)RR gene may induce atrial fibrillation by activation of Erk1/2 in the cardiac fibroblasts of the atria. (p)RR promotes atrial structural and electrical remodeling in vivo, which indicates that (p)RR plays an important role in the pathological development of AF. Copyright © 2015. Published by Elsevier Ireland Ltd.

A Study on Plasma Renin Activity in Korean Hemorrhagic Fever

International Nuclear Information System (INIS)

Kim, Suhng Gwon; Cho, Bo Yun; Lee, Jung Sang; Koh, Won Soon; Lee, Mun Ho; Kim, Won Dong; Yun, Hong Jin

1976-01-01

To evaluate the possible pathophysiologic role of renin in acute renal failure observed in Korean hemorrhagic fever (KHF), the author measured the basal plasma renin activity (PRA) and the stimulated PRA by radioimmunoassay for angiotensin I in 15 normal controls and 42 KHF patients who are admitted in Seoul National University Hospital and Nation Army Hospital from Jan. 1975 to Jan. 1976. The results obtained were as follows:The mean basal PRA in normal control group was 2.9±2.16 ng/ml/hr in the patients during the oliguric phase of KHF, the mean basal PRA was 4.7±2.13 ng/ml/hr, and there was statistically significant increase compared to the normal control. In the patients during the diuretic phase of KHF, the mean basal PRA was 3.4±2.09 ng/ml/hr, and there was statistically significant decrease compared to the oliguric phase of KHF. In normal control group, the mean basal PRA was 2.9±2.16 ng/ml/hr. And the PRA 1 hour after the administration of Lasix 40 mg intravenously (stimulated PRA) was 5.3±2.20 ng/ml/hr and there was statistically significant increase compared to basal level. In oliguric phase of KHF, the mean basal PRA was 4.6±2.01 ng/ml/hr. And stimulated PRA was 4.4±2.34 ng/ml/hr and there was no significant changes. In diuretic phase of KHF, the mean basal PR was 3.3±1.86 ng/ml/hr. And stimulated PRA was 5.2±2.58 ng/ml/hr and there was statistically significant increase compared to basal level. There were statistically no significant correlations between basal PRA and stimulated PRA and serum creatinine. BUN, urine volume and peritoneal dialysis.

Expression of renin-angiotensin system signalling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure.

Science.gov (United States)

Mesquita, Flávia Fernandes; Gontijo, José Antonio Rocha; Boer, Patrícia Aline

2010-02-01

Intrauterine growth restriction due to low maternal dietary protein during pregnancy is associated with retardation of foetal growth, renal alterations and adult hypertension. The renin-angiotensin system (RAS) is a coordinated hormonal cascade in the control of cardiovascular, renal and adrenal function that governs body fluid and electrolyte balance, as well as arterial pressure. In the kidney, all the components of the renin-angiotensin system including angiotensin II type 1 (AT1) and type 2 (AT2) receptors are expressed locally during nephrogenesis. Hence, we investigated whether low protein diet intake during pregnancy altered kidney and adrenal expression of AT1(R) and AT2(R) receptors, their pathways and if the modified expression of the RAS compounds occurs associated with changes in urinary sodium and in arterial blood pressure in sixteen-week-old males' offspring of the underfed group. The pregnancy dams were divided in two groups: with normal protein diet (pups named NP) (17% protein) or low protein diet (pups LP) (6% protein) during all pregnancy. The present data confirm a significant enhancement in arterial pressure in the LP group. Furthermore, the study showed a significantly decreased expression of RAS pathway protein and Ang II receptors in the kidney and an increased expression in the adrenal of LP rats. The detailed immunohistochemical analysis of RAS signalling proteins in the kidney confirm the immunoblotting results for both groups. The present investigation also showed a pronounced decrease in fractional urinary sodium excretion in maternal protein-restricted offspring, compared with the NP age-matched group. This occurred despite unchanged creatinine clearance. The current data led us to hypothesize that foetal undernutrition could be associated with decreased kidney expression of AT(R) resulting in the inability of renal tubules to handle the hydro-electrolyte balance, consequently causing arterial hypertension.

Renin-Angiotensin System Blockade Improves Cardiac Indices in Acromegaly Patients.

Science.gov (United States)

Thomas, Julia D J; Dattani, Abhishek; Zemrak, Filip; Burchell, Thomas; Akker, Scott A; Kaplan, Felicity J L; Khoo, Bernard; Aylwin, Simon; Grossman, Ashley B; Davies, L Ceri; Korbonits, Márta

2017-06-01

Blockade of the angiotensin-renin system, with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), has been shown to improve cardiac outcomes following myocardial infarction and delay progression of heart failure. Acromegaly is associated with a disease-specific cardiomyopathy, the pathogenesis of which is poorly understood.The cardiac indices of patients with active acromegaly with no hypertension (Group A, n=4), established hypertension not taking ACEi/ARBs (Group B, n=4) and established hypertension taking ACEi/ARBs (Group C, n=4) were compared using cardiac magnetic imaging.Patients taking ACEi/ARBs had lower end diastolic volume index (EDVi) and end systolic volume index (ESVi) than the other 2 groups ([C] 73.24 vs. [A] 97.92 vs. [B] 101.03 ml/m 2 , ANOVA p=0.034, B vs. C pAcromegaly patients on ACEi/ARBs for hypertension demonstrate improved cardiac indices compared to acromegaly patients with hypertension not taking these medications. Further studies are needed to determine if these drugs have a beneficial cardiac effect in acromegaly in the absence of demonstrable hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

Erythrocyte 2,3-diphosphoglycerate and serum enzyme concentrations in trained and sedentary men.

Science.gov (United States)

Lijnen, P; Hespel, P; Van Oppens, S; Fiocchi, R; Goossens, W; Vanden Eynde, E; Amery, A

1986-04-01

The acute effect of exercise on the intraerythrocyte 2,3-diphosphoglycerate concentration and on various serum enzymes and some related variables was investigated in 14 male athletes before and after a 50-min cross-country run and compared at rest to 15 sedentary subjects. Compared to the sedentary subjects, the athletes had higher resting levels of serum creatine phosphokinase, plasma myoglobin, and renin substrate but had a lower plasma renin activity. The red blood cell 2,3-diphosphoglycerate concentration increased after exercise in the runners and was not different at rest between the athletes and the sedentary subjects. Our data therefore suggest that the resting plasma renin activity is reduced in athletes when compared to sedentary subjects. Training seems however not to alter the resting level of 2,3-diphosphoglycerate in the red blood cells.

Study of the components of renin-angiotensinaldosterone system and KalliKrein -Kinin system in normal pregnancy

International Nuclear Information System (INIS)

Abreu Fagundes, V.G. de.

1984-01-01

The alterations in the renin-angiotensin-aldosterone system and Kallikrein-Kinin system were studied. The possible interferences of these systems on the arterial pressure and on the evolution of normal pregnancy were presented in the following situations: when the pregnant change from dorsal decumbency to left lateral decumbency and to orthostatic position. (M.A.C.) [pt

Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage

DEFF Research Database (Denmark)

Lachmann, Peter; Hickmann, Linda; Steglich, Anne

2017-01-01

Intracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility...... in the maintenance and protection of the renal microvascular endothelium....

Impact of substrate on performance of band gap engineered graphene field effect transistor

Science.gov (United States)

Tiwari, Durgesh Laxman; Sivasankaran, K.

2018-01-01

In this paper, we investigate the graphene field effect transistor (G-FET) to enhance the drain current saturation and to minimize the drain conductance (gd) using numerical simulation. This work focus on suppressing the drain conductance using silicon substrate. We studied the impact of different substrate on the performance of band gap engineered G-FET device. We used a non-equilibrium green function with mode space (NEGF_MS) to model the transport behavior of carriers for 10 nm channel length G-FET device. We compared the drain current saturation of G-FET at higher drain voltage regime on silicon, SiC, and the SiO2 substrate. This paper clearly demonstrates the effect of substrate on an electric field near drain region of G-FET device. It is shown that the substrate of G-FET is not only creating a band gap in graphene, which is important for current saturation and gd minimization, but also selection of suitable substrate can suppress generation of carrier concentration near drain region is also important.

Effects of beam, target and substrate potentials in ion beam processing

International Nuclear Information System (INIS)

Harper, J.M.E.

1982-01-01

Ion beam etching and deposition are normally carried out with beam, target and substrate potentials near ground potential. In this paper, the effects of intentional or unintentional changes in these potentials are described. Examples include beam neutralization, a single extraction grid, substrate bias, and target bias. Each example is described in terms of beam plasma parameters. (Auth.)

Collective ratchet effects and reversals for active matter particles on quasi-one-dimensional asymmetric substrates.

Science.gov (United States)

McDermott, Danielle; Olson Reichhardt, Cynthia J; Reichhardt, Charles

2016-10-19

Using computer simulations, we study a two-dimensional system of sterically interacting self-mobile run-and-tumble disk-shaped particles with an underlying periodic quasi-one-dimensional asymmetric substrate, and show that a rich variety of collective active ratchet behaviors arise as a function of particle density, activity, substrate period, and the maximum force exerted by the substrate. The net dc drift, or ratchet transport flux, is nonmonotonic since it increases with increased activity but is diminished by the onset of self-clustering of the active particles. Increasing the particle density decreases the ratchet transport flux for shallow substrates but increases the ratchet transport flux for deep substrates due to collective hopping events. At the highest particle densities, the ratchet motion is destroyed by a self-jamming effect. We show that it is possible to realize reversals of the direction of the net dc drift in the deep substrate limit when multiple rows of active particles can be confined in each substrate minimum, permitting emergent particle-like excitations to appear that experience an inverted effective substrate potential. We map out a phase diagram of the forward and reverse ratchet effects as a function of the particle density, activity, and substrate properties.

Effect of Substrate Permittivity and Thickness on Performance of Single-Layer, Wideband, U-Slot Antennas on Microwave Substrates

National Research Council Canada - National Science Library

Natarajan, V; Chatterjee, D

2004-01-01

This paper presents effects of substrate permittivity and thickness on the performance characteristics like impedance bandwidth, radiation efficiency and gain of a single-layer, wideband, U-slot antenna...

Synthesis of tritium labeled renin inhibitor ditekiren

International Nuclear Information System (INIS)

Hsi, R.S.P.; Stolle, W.T.; Bundy, G.L.

1994-01-01

In the search for a radioactive form of the peptidomimetic renin inhibitor, ditekiren, with a metabolically suitable radiolabel for conducting drug disposition studies, we prepared [ 3 H]ditekiren with tritium labels in the N-methyl-histidine moiety and in the leu-val alcohol transition-state insert. [His- 3 H]ditekiren was obtained by first introducing two iodine substituents into the N-methyl-histidine moiety of the parent drug, followed by catalytic hydrodehalogenation with tritium gas. Administration of this labeled drug to monkeys, however, resulted in prolonged retention of radioactivity in the test animals, even though little or no tritiated water was detected in urine. The results, together with similar earlier findings after administration of [ 3 H]ditekiren labeled in the proline moiety of the drug, led us to synthesize [ 3 H]ditekiren labeled in the ''unnatural'' leu-val alcohol (LVA) portion of the molecule. The tritium label in [LVA- 3 H]ditekiren was found to be metabolically suitable for conducting drug disposition studies, with no liability for tritiated water production or prolonged retention of radioactivity in tissues of test animals. (author)

Effects of heavy metals on enzyme synthesis in substrate-amended river sediments

Energy Technology Data Exchange (ETDEWEB)

Wainwright, M; Duddridge, J E

1982-01-01

The effects of heavy metals in diverse substrate-amended river sediments were studied. Cd/sup 2 +/, Pb/sup 2 +/ and Zn/sup 2 +/ generally had a marked inhibitory effect on the synthesis of amylase, cellulase and urease, on numbers of substrate-hydrolysing bacteria, in all sediments studied. Inhibition increased with increasing metal concentration, and amylase was particularly sensitive. Pb/sup 2 +/ generally had the least effect. We conclude that enzyme synthesis measurements are useful in determining the effects of heavy metals on the degradation of organic pollutants in river sediments.

Effect of Trichoderma on horticultural seedlings' growth promotion depending on inoculum and substrate type.

Science.gov (United States)

Marín-Guirao, J I; Rodríguez-Romera, P; Lupión-Rodríguez, B; Camacho-Ferre, F; Tello-Marquina, J C

2016-10-01

The biostimulant effect of Trichoderma spp. on horticultural crops are highly variable. Thus, practical use of Trichoderma sp. requires feasible formulated products and suitable substrates. This study evaluates the survival and the growth-promotion effect of a Trichoderma saturnisporum rice formulation compared with a nonformulated conidia suspension (seven treatments in total), on tomato, pepper and cucumber seedlings grown in two substrates: (i) rich in organic matter (OM) and (ii) mineral substrate without OM. The results showed beneficial effects on seedling growth in the OM-rich substrate when T. saturnisporum rice formulation (mainly at maximum concentration) was applied, but the effects were opposite when the mineral substrate without OM was used. The effects were closely linked to the level of inoculum in the substrate, which was greater upon application of the formulated inoculum as opposed to the nonformulated one. The use of rice to prepare the inoculum of T. saturnisporum seems to be promising for seedling growth in the nursery when it is applied in a substrate that is rich in organic matter, but it must be considered that under certain conditions of food shortage, Trichoderma sp. could show pathogenicity to seedlings. This study provides evidence of the complexity inherent in the use of micro-organisms in agriculture, while also confirming that the activity of the biofertilizers based on Trichoderma depends on the type of inoculum and its concentration, as well as the properties of the medium in which the fungi develop. Further studies assessing the effectiveness or possible pathogenicity of Trichoderma in different soils under greenhouse conditions must be addressed. © 2016 The Society for Applied Microbiology.

Effects of Ganoderma lucidum Spent Mushroom Substrate Extract on ...

African Journals Online (AJOL)

Effects of Ganoderma lucidum Spent Mushroom Substrate Extract on Milk and ... Serum antioxidant activity as well as milk and serum immunoglobulin levels were ... total antioxidant capacity (TAC) and mean serum TAC concentration among ...

Effect of substrates on tribological properties of diamond-like carbon coating

Directory of Open Access Journals (Sweden)

Renhui ZHANG

2017-06-01

Full Text Available In order to well investigate the effect of different substrates on the friction and wear of diamond-like carbon (DLC coating, the DLC coatings are deposited on substrates like the high-speed steel (HSS, SiC and 304 stainless steel by using plasma enhanced chemical vapor deposition method. The diamond-like carbon is prepared. The microstructure of the coatings is characterized using SEM, TEM and Raman. The SEM results exhibit that the total thickness of the coatings is about 6.5 μm, and there's apparent interfaces between layers. The TEM results imply that the coatings have an amorphous structure. Raman spectrum exhibits that G and D peaks are observed, which implies that the deposition coatings are diamond-like carbon coating. The results of tribological tests show that the substrates have a significant effect on the friction and wear of the coating. For different substrates, the transfer film is found on the steel counterpart surface, the wear track of the HSS has a lowest width, and the DLC coating that deposited on HSS exhibits the lowest wear and low friction coefficient (about 0.1.The microstructure of different substrates wear track surfaces is analyzed by using Raman spectrum, and the lowest wear of the HSS is attributed to the lower degree of the graphitization. The research provides reference for preparing the DLC coating with excellent tribological properties.

Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.

Science.gov (United States)

Li, Jianchang; Qiu, Mingning; Chen, Lieqian; Liu, Lei; Tan, Guobin; Liu, Jianjun

2017-02-01

The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

Directory of Open Access Journals (Sweden)

Stanslas Johnson

2009-02-01

Full Text Available Abstract Background The renin-angiotensin aldosterone system (RAAS plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT, MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects. Methods RAAS gene polymorphisms were determined using mutagenically separated PCR and PCR-RFLP method in a total of 270 subjects consisting of 70 hypertensive subjects without type 2 diabetes mellitus (T2DM, 60 T2DM, 65 hypertensive subjects with T2DM and 75 control subjects. Results There was significant difference found in age, body mass index, systolic/diastolic blood pressure, fasting plasma glucose and high density lipoprotein cholesterol levels between the hypertensive subjects with or without T2DM and control subjects. No statistically significant differences between groups were found in the allele frequency and genotype distribution for A20C variant of AGT gene, MboI of renin, Gly460Trp of aldosterone and Lys173Arg of adducin (p > 0.05. However, the results for A6G of AGT gene revealed significant differences in allele and genotype frequencies in essential hypertension with or without T2DM (p Conclusion Among the five polymorphisms of RAAS genes only A6G variant of AGT gene was significantly associated in Malaysian essential hypertensive and type 2 diabetic subjects. Therefore, A6G polymorphism of the AGT gene could be a potential genetic marker for increased susceptibility to essential hypertension with or without T2DMin Malaysian subjects.

The effect of optical substrates on micro-FTIR analysis of single mammalian cells.

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Wehbe, Katia; Filik, Jacob; Frogley, Mark D; Cinque, Gianfelice

2013-02-01

The study of individual cells with infrared (IR) microspectroscopy often requires living cells to be cultured directly onto a suitable substrate. The surface effect of the specific substrates on the cell growth-viability and associated biochemistry-as well as on the IR analysis-spectral interference and optical artifacts-is all too often ignored. Using the IR beamline, MIRIAM (Diamond Light Source, UK), we show the importance of the substrate used for IR absorption spectroscopy by analyzing two different cell lines cultured on a range of seven optical substrates in both transmission and reflection modes. First, cell viability measurements are made to determine the preferable substrates for normal cell growth. Successively, synchrotron radiation IR microspectroscopy is performed on the two cell lines to determine any genuine biochemically induced changes or optical effect in the spectra due to the different substrates. Multivariate analysis of spectral data is applied on each cell line to visualize the spectral changes. The results confirm the advantage of transmission measurements over reflection due to the absence of a strong optical standing wave artifact which amplifies the absorbance spectrum in the high wavenumber regions with respect to low wavenumbers in the mid-IR range. The transmission spectra reveal interference from a more subtle but significant optical artifact related to the reflection losses of the different substrate materials. This means that, for comparative studies of cell biochemistry by IR microspectroscopy, it is crucial that all samples are measured on the same substrate type.

Low-voltage self-assembled monolayer field-effect transistors on flexible substrates.

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Schmaltz, Thomas; Amin, Atefeh Y; Khassanov, Artoem; Meyer-Friedrichsen, Timo; Steinrück, Hans-Georg; Magerl, Andreas; Segura, Juan José; Voitchovsky, Kislon; Stellacci, Francesco; Halik, Marcus

2013-08-27

Self-assembled monolayer field-effect transistors (SAMFETs) of BTBT functionalized phosphonic acids are fabricated. The molecular design enables device operation with charge carrier mobilities up to 10(-2) cm(2) V(-1) s(-1) and for the first time SAMFETs which operate on rough, flexible PEN substrates even under mechanical substrate bending. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The protective arm of the renin-angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves.

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Rocha, Natalia P; Bastos, Fernando M; Vieira, Érica L M; Prestes, Thiago R R; Silveira, Katia D da; Teixeira, Mauro M; Simões E Silva, Ana Cristina

2018-03-11

Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme-linked immunosorbent assay. Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang-(1-7) and angiotensin-converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Prospective validation of an automated chemiluminescence-based assay of renin and aldosterone for the work-up of arterial hypertension.

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Rossi, Gian Paolo; Ceolotto, Giulio; Rossitto, Giacomo; Seccia, Teresa Maria; Maiolino, Giuseppe; Berton, Chiara; Basso, Daniela; Plebani, Mario

2016-09-01

The availability of simple and accurate assays of plasma active renin (DRC) and aldosterone concentration (PAC) can improve the detection of secondary forms of arterial hypertension. Thus, we investigated the performance of an automated chemiluminescent assay for DRC and PAC in referred hypertensive patients. We prospectively recruited 260 consecutive hypertensive patients referred to an ESH Center for Hypertension. After exclusion of six protocol violations, 254 patients were analyzed: 67.3% had primary hypertension, 17.3% an aldosterone producing adenoma (APA), 11.4% idiopathic hyperaldosteronism (IHA), 2.4% renovascular hypertension (RVH), 0.8% familial hyperaldosteronism type 1 (FH-1), 0.4% apparent mineralocorticoid excess (AME), 0.4% a renin-producing tumor, and 3.9% were adrenalectomized APA patients. Bland-Altman plots and Deming regression were used to analyze results. The diagnostic accuracy (area under the curve, AUC of the ROC) of the DRC-based aldosterone-renin ratio (ARRCL) was compared with that of the PRA-based ARR (ARRRIA) using as reference the conclusive diagnosis of APA. At Bland-Altman plot, the DRC and PAC assay showed no bias as compared to the PRA and PAC assay. A tight relation was found between the DRC and the PRA values (concordance correlation coefficient=0.92, pAPA identification the AUC of the ARRCL was higher than that of the ARRRIA [0.974 (95% CI 0.940-0.991) vs. 0.894 (95% CI 0.841-0.933), p=0.02]. This rapid automated chemiluminescent DRC/PAC assay performed better than validated PRA/PAC radioimmunoassays for the identification of APA in referred hypertensive patients.

Isotope-edited proton NMR study on the structure of a pepsin/inhibitor complex

International Nuclear Information System (INIS)

Fesik, S.W.; Luly, J.R.; Erickson, J.W.; Abad-Zapatero, C.

1988-01-01

A general approach is illustrated for providing detailed structural information on large enzyme/inhibitor complexes using NMR spectroscopy. The method involves the use of isotopically labeled ligands to simplify two-dimensional NOE spectra of large molecular complexes by isotope-editing techniques. With this approach, the backbone and side-chain conformations (at the P 2 and P 3 sites) of a tightly bound inhibitor of porcine pepsin have bene determined. In addition, structural information on the active site of pepsin has been obtained. Due to the sequence homology between porcine pepsin and human renin, this structural information may prove useful for modeling renin/inhibitor complexes with the ultimate goal of designing more effective renin inhibitors. Moreover, this general approach can be applied to study other biological systems of interest such as other enzyme/inhibitor complexes, ligands bound to soluble receptors, and enzyme/substrate interactions

Wafer-Scale Gigahertz Graphene Field Effect Transistors on SiC Substrates

Institute of Scientific and Technical Information of China (English)

潘洪亮; 金智; 麻芃; 郭建楠; 刘新宇; 叶甜春; 李佳; 敦少博; 冯志红

2011-01-01

Wafer-scale graphene field-effect transistors are fabricated using benzocyclobutene and atomic layer deposition Al2O3 as the top-gate dielectric.The epitaxial-graphene layer is formed by graphitization of a 2-inch-diameter Si-face semi-insulating 6H-SiC substrate.The graphene on the silicon carbide substrate is heavily n-doped and current saturation is not found.For the intrinsic characteristic of this particular channel material,the devices cannot be switched off.The cut-off frequencies of these graphene field-effect transistors,which have a gate length of l μm,are larger than 800 MHz.The largest one can reach 1.24 GHz.There are greater than 95％ active devices that can be successfully applied.We thus succeed in fabricating wafer-scale gigahertz graphene field-effect transistors,which paves the way for high-performance graphene devices and circuits.%Wafer-scale graphene Beld-effect transistors are fabricated using benzocyclobutene and atomic layer deposition AI2O3 as the top-gate dielectric. The epitaxial-graphene layer is formed by graphitization of a 2-inch-diameter Si-face semi-insulating 6H-SiC substrate. The graphene on the silicon carbide substrate is heavily n-doped and current saturation is not found. For the intrinsic characteristic of this particular channel material, the devices cannot be switched off. The cut-off frequencies of these graphene field-effect transistors, which have a gate length of l μm, are larger than 800MHz. The largest one can reach 1.24 GHz. There are greater than 95% active devices that can be successfully applied. We thus succeed in fabricating wafer-scale gigahertz graphene Geld-effect transistors, which paves the way for high-performance graphene devices and circuits.

Theory of magnetoelectric effect in multilayer nanocomposites on a substrate: Resonant bending-mode response

Directory of Open Access Journals (Sweden)

Matthias C. Krantz

2013-05-01

Full Text Available Resonant bending-mode magnetoelectric (ME coefficients of magnetostrictive-piezoelectric multilayer cantilevers are calculated analytically using a model developed for arbitrary multilayers on a substrate. Without quality factor effects the ME coefficient maxima in the four-dimensional parameter space of layer numbers, layer sequences, piezoelectric volume fractions, and substrate thicknesses are found to be essentially constant for nonzero substrate thickness. Global maxima occur for bilayers without substrates. Vanishing magnetoelectric response regions result from voltage cancellation in piezoelectric layers or absence of bending-mode excitation. They are determined by the neutral plane position in the multilayer stack. With Q-factor effects dominated by viscous air damping ME coefficients strongly increase with cantilever thickness primarily due to increasing resonance frequencies. The results yield a layer specific prediction of ME coefficients, resonance frequencies, and Q-factors in arbitrary multilayers and thus distinction of linear-coupling and Q-factor effects from exchange interaction, interface, or nonlinear ME effects.

Nephroprotective action of renin-angiotensin-aldosterone system blockade in chronic kidney disease patients: the landscape after ALTITUDE and VA NEPHRON-D trails.

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Rutkowski, Boleslaw; Tylicki, Leszek

2015-03-01

The intervention in the renin-angiotensin-aldosterone system (RAAS) is currently the most effective strategy that combines blood pressure lowering and renoprotection. Several large, randomized, controlled trials evidenced the renoprotective potential of the angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in nephropathies of almost any etiology. Mineralocorticoid receptor antagonists and direct renin inhibitor, aliskiren, as add-on treatments to standard therapy including the optimal dose of ACEIs or ARBs reduce albuminuria or proteinuria and slow development of renal dysfunction more than placebo. No clinical evidence is available however about whether these strategies may influence on long-term kidney outcome. Three recent trials suggested that aggressive RAAS blockade, that is, combination of 2 RAAS-blocking agents, does not decrease cardiovascular and renal morbidity and may carry an increased risk of serious complications. This article reviews an evidence-based approach on the use of RAAS-inhibiting agents in chronic kidney disease and considers the implementation of dual RAAS blockade with reference to the results of ALTITUDE and VA NEPHRON-D trails aiming to aid clinicians in their treatment decisions for patients with chronic kidney disease. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

A Mixed-Ligand Approach Enables the Asymmetric Hydrogenation of an α-Isopropylcinnamic Acid en Route to the Renin Inhibitor Aliskiren

NARCIS (Netherlands)

Boogers, Jeroen A.F.; Felfer, Ulfried; Kotthaus, Martina; Lefort, Laurent; Steinbauer, Gerhard; Vries, André H.M. de; Vries, Johannes G. de

2007-01-01

An asymmetric hydrogenation process for an α-isopropyl dihydrocinnamic acid derivative, an intermediate for the renin inhibitor aliskiren, has been developed using a rhodium catalyst ligated with a chiral monodentate phosphoramidite and a nonchiral phosphine. Whereas catalysts based on two

Effect of External Electric Field on Substrate Transport of a Secondary Active Transporter.

Science.gov (United States)

Zhang, Ji-Long; Zheng, Qing-Chuan; Yu, Li-Ying; Li, Zheng-Qiang; Zhang, Hong-Xing

2016-08-22

Substrate transport across a membrane accomplished by a secondary active transporter (SAT) is essential to the normal physiological function of living cells. In the present research, a series of all-atom molecular dynamics (MD) simulations under different electric field (EF) strengths was performed to investigate the effect of an external EF on the substrate transport of an SAT. The results show that EF both affects the interaction between substrate and related protein's residues by changing their conformations and tunes the timeline of the transport event, which collectively reduces the height of energy barrier for substrate transport and results in the appearance of two intermediate conformations under the existence of an external EF. Our work spotlights the crucial influence of external EFs on the substrate transport of SATs and could provide a more penetrating understanding of the substrate transport mechanism of SATs.

Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes.

Science.gov (United States)

Shin, Seok Joon; Chung, Sungjin; Kim, Soo Jung; Lee, Eun-Mi; Yoo, Young-Hye; Kim, Ji-Won; Ahn, Yu-Bae; Kim, Eun-Sook; Moon, Sung-Dae; Kim, Myung-Jun; Ko, Seung-Hyun

2016-01-01

Renal renin-angiotensin system (RAS) activation is one of the important pathogenic mechanisms in the development of diabetic nephropathy in type 2 diabetes. The aim of this study was to investigate the effects of a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, dapagliflozin, on renal RAS in an animal model with type 2 diabetes. Dapagliflozin (1.0 mg/kg, OL-DA) or voglibose (0.6 mg/kg, OL-VO, diabetic control) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats for 12 weeks. We used voglibose, an alpha-glucosidase inhibitor, as a comparable counterpart to SGLT2 inhibitor because of its postprandial glucose-lowering effect without proven renoprotective effects. Control Long-Evans Tokushima Otsuka (LT) and OLETF (OL-C) rats received saline (n = 10, each). Changes in blood glucose, urine albumin, creatinine clearance, and oxidative stress were measured. Inflammatory cell infiltration, mesangial widening, and interstitial fibrosis in the kidney were evaluated by histological analysis. The effects of dapagliflozin on renal expression of the RAS components were evaluated by quantitative RT-PCR in renal tissue. After treatment, hyperglycemia and urine microalbumin levels were attenuated in both OL-DA and OL-VO rather than in the OL-C group (P renal RAS component expression, oxidative stress and interstitial fibrosis in OLETF rats. We suggest that, in addition to control of hyperglycemia, partial suppression of renal RAS with an SGLT2 inhibitor would be a promising strategy for the prevention of treatment of diabetic nephropathy.

Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs.

Science.gov (United States)

Ames, Marisa K; Atkins, Clarke E; Lee, Seunggon; Lantis, Andrea C; zumBrunnen, James R

2015-12-01

To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS). 6 healthy Beagles. 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days -1, 3, and 7; serum aldosterone concentration on days -2, -1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days -2, -1, 1, 3, and 7. High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C. In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.

The Effect of Substrate Elasticity and Actomyosin Contractility on Different Forms of Endocytosis

Science.gov (United States)

Missirlis, Dimitris

2014-01-01

Substrate mechanical properties have emerged as potent determinants of cell functions and fate. We here tested the hypothesis that different forms of endocytosis are regulated by the elasticity of the synthetic hydrogels cells are cultured on. Towards this objective, we quantified cell-associated fluorescence of the established endocytosis markers transferrin (Tf) and cholera toxin subunit B (CTb) using a flow-cytometry based protocol, and imaged marker internalization using microscopy techniques. Our results demonstrated that clathrin-mediated endocytosis of Tf following a 10-minute incubation with a fibroblast cell line was lower on the softer substrates studied (5 kPa) compared to those with elasticities of 40 and 85 kPa. This effect was cancelled after 1-hour incubation revealing that intracellular accumulation of Tf at this time point did not depend on substrate elasticity. Lipid-raft mediated endocytosis of CTb, on the other hand, was not affected by substrate elasticity in the studied range of time and substrate elasticity. The use of pharmacologic contractility inhibitors revealed inhibition of endocytosis for both Tf and CTb after a 10-minute incubation and a dissimilar effect after 1 hour depending on the inhibitor type. Further, the internalization of fluorescent NPs, used as model drug delivery systems, showed a dependence on substrate elasticity, while transfection efficiency was unaffected by it. Finally, an independence on substrate elasticity of Tf and CTb association with HeLa cells indicated that there are cell-type differences in this respect. Overall, our results suggest that clathrin-mediated but not lipid-raft mediated endocytosis is potentially influenced by substrate mechanics at the cellular level, while intracellular trafficking and accumulation show a more complex dependence. Our findings are discussed in the context of previous work on how substrate mechanics affect the fundamental process of endocytosis and highlight important

Renin-angiotensin system: an old player with novel functions in skeletal muscle.

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Cabello-Verrugio, Claudio; Morales, María Gabriela; Rivera, Juan Carlos; Cabrera, Daniel; Simon, Felipe

2015-05-01

Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle. © 2015 Wiley Periodicals, Inc.

Alternate substrates and isotope effects as a probe of the malic enzyme reaction

International Nuclear Information System (INIS)

Gavva, S.R.

1988-01-01

Dissociation constants for alternative dinucleotide substrates and competitive inhibitors suggest that the dinucleotide binding site of the Ascaris suum NAD-malic enzyme is hydrophobic in the vicinity of the nicotinamide ring. Changes in the divalent metal ion activator from Mg 2+ to Mn 2+ or Cd 2+ results in a decrease in the dinucleotide affinity and an increase in the affinity for malate. Primary deuterium and 13 C isotope effects obtained with the different metal ions suggest either a change in the transition state structure for the hydride transfer or decarboxylation steps or both. Deuterium isotope effects are finite whether reactants are maintained at saturating or limiting concentrations with all the metal ions and dinucleotide substrates used. For the native enzyme, primary deuterium isotope effects increase with a concomitant decrease in the 13 C effects when NAD is replaced by an alternate dinucleotide substrate different in redox potential

Epitaxial growth mechanisms of graphene and effects of substrates

Science.gov (United States)

Özçelik, V. Ongun; Cahangirov, S.; Ciraci, S.

2012-06-01

The growth process of single layer graphene with and without substrate is investigated using ab initio, finite temperature molecular dynamic calculations within density functional theory. An understanding of the epitaxial graphene growth mechanisms in the atomic level is provided by exploring the transient stages which occur at the growing edges of graphene. These stages are formation and collapse of large carbon rings together with the formation and healing of Stone-Wales like pentagon-heptagon defects. The activation barriers for the healing of these growth induced defects on various substrates are calculated using the climbing image nudge elastic band method and compared with that of the Stone-Wales defect. It is found that the healing of pentagon-heptagon defects occurring near the edge in the course of growth is much easier than that of Stone-Wales defect. The role of the substrate in the epitaxial growth and in the healing of defects are also investigated in detail, along with the effects of using carbon dimers as the building blocks of graphene growth.

Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

Science.gov (United States)

Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

2010-01-01

The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

Effects of substrates on biofilm formation observed by atomic force microscopy

International Nuclear Information System (INIS)

Oh, Y.J.; Lee, N.R.; Jo, W.; Jung, W.K.; Lim, J.S.

2009-01-01

Formation of biofilm is known to be strongly dependent on substrates including topography, materials, and chemical treatment. In this study, a variety of substrates are tested for understanding biofilm formation. Sheets of aluminum, steel, rubber, and polypropylene have been used to examine their effects on formation of Pseudomonas aeruginosa biofilm. In particular, the morphological variation, transition, and adhesiveness of biofilm were investigated through local measurement by atomic force microscopy (AFM). Mechanism of removing biofilm from adhering to substrate is also analyzed, thus the understanding of the mechanism can be potentially useful to prevent the biofilm formation. The results reveal that formation of biofilm can remain on rough surface regardless of substrates in hot water, which may easily induce extra-polymeric substances detachment from bacterial surface. By probing using AFM, local force-distance characterization of extra-cellular materials extracted from the bacteria can exhibit the progress of the biofilm formation and functional complexities.

Palmitoylethanolamide treatment reduces blood pressure in spontaneously hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin angiotensin system.

Directory of Open Access Journals (Sweden)

Giuseppina Mattace Raso

Full Text Available Palmitoylethanolamide (PEA, a peroxisome proliferator-activated receptor-α agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR. Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF, and renin angiotensin system (RAS modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the

Clamping effect on the piezoelectric responses of screen-printed low temperature PZT/Polymer films on flexible substrates

Science.gov (United States)

Almusallam, A.; Yang, K.; Zhu, D.; Torah, R. N.; Komolafe, A.; Tudor, J.; Beeby, S. P.

2015-11-01

This paper introduces a new flexible lead zirconate titanate (PZT)/polymer composite material that can be screen-printed onto fabrics and flexible substrates, and investigates the clamping effect of these substrates on the characterization of the piezoelectric material. Experimental results showed that the optimum blend of PZT/polymer binder with a weight ratio of 12:1 provides a dielectric constant of 146. The measured value of the piezoelectric coefficient d33 was found to depend on the substrate used. Measured d33clp values of 70, 40, 36 pC N-1 were obtained from the optimum formulation printed on Polyester-cotton with an interface layer, Kapton and alumina substrates, respectively. The variation in the measured d33clp values occurs because of the effect of the mechanical boundary conditions of the substrate. The piezoelectric film is mechanically bonded to the surface of the substrate and this constrains the film in the plane of the substrate (the 1-direction). This constraint means that the perpendicular forces (applied in the 3-direction) used to measure d33 introduce a strain in the 1-direction that produces a charge of the opposite polarity to that induced by the d33 effect. This is due to the negative sign of the d31 coefficient and has the effect of reducing the measured d33 value. Theoretical and experimental investigations confirm a reduction of 13%, 50% and 55% in the estimated freestanding d33fs values (80 pC N-1) on Polyester-cotton, Kapton and alumina substrates, respectively. These results demonstrate the effect of the boundary conditions of the substrate/PZT interface on the piezoelectric response of the PZT/polymer film and in particular the reduced effect of fabric substrates due to their lowered stiffness.

Irradiation effects of Ar cluster ion beams on Si substrates

International Nuclear Information System (INIS)

Ishii, Masahiro; Sugahara, Gaku; Takaoka, G.H.; Yamada, Isao

1993-01-01

Gas-cluster ion beams can be applied to new surface modification techniques such as surface cleaning, low damage sputtering and shallow junction formation. The effects of energetic Ar cluster impacts on solid surface were studied for cluster energies of 10-30keV. Irradiation effects were studied by RBS. For Si(111) substrates, irradiated with Ar ≥500 clusters to a dose of 1x10 15 ion/cm 2 at acceleration voltage 15kV, 2x10 14 atoms/cm 2 implanted Ar atoms were detected. In this case, the energy per cluster atom was smaller than 30eV; at this energy, no significant implantation occurs in the case of monomer ions. Ar cluster implantation into Si substrates occurred due to the high energy density irradiation. (author)

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

DEFF Research Database (Denmark)

Leyssac, P P; Holstein-Rathlou, N H; Skøtt, O

2000-01-01

.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), ED......(NaCl) increased by 3.6 mM, (P renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 micromol NaCl in a smaller volume caused ED(NaCl) to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly...

Substrate specific effects of calcium on metabolism of rat heart mitochondria.

Science.gov (United States)

Panov, A V; Scaduto, R C

1996-04-01

Oxidative metabolism in the heart is tightly coupled to mechanical work. Because this coupling process is believed to involve Ca2+, the roles of mitochondrial Ca2+ in the regulation of oxidative phosphorylation was studied in isolated rat heart mitochondria. The electrical component of the mitochondrial membrane potential (delta psi) and the redox state of the pyridine nucleotides were determined during the oxidation of various substrates under different metabolic states. In the absence of added adenine nucleotides, the NADP+ redox couple was almost completely reduced, regardless of the specific substrate and the presence of Ca2+, whereas NAD+ couple redox state was highly dependent on the substrate type and the presence of Ca2+. Titration of respiration with ADP, in the presence of excess hexokinase and glucose, showed that both respiration and NAD(P)+ reduction were very sensitive to ADP. The maximal enzyme reaction rate of ADP-stimulated respiration Michaelis constants (Km) for ADP were dependent on the particular substrate employed. delta psi was much less sensitive to ADP. With either alpha-ketoglutarate or glutamate as substrate, Ca2+ significantly increased reduction of NAD(P)+.Ca2+ did not influence NAD(P)+ reduction with either acetylcarnitine or pyruvate as substrate. In the presence of ADP, delta psi was increased by Ca2+ at all metabolic states with glutamate plus malate, 0.5 mM alpha-ketoglutarate plus malate, or pyruvate plus malate as substrates. The data presented support the hypothesis that cardiac respiration is controlled by the availability of both Ca2+ and ADP to mitochondria. The data indicate that an increase in substrate supply to mitochondria can increase mitochondrial respiration at given level of ADP. This effect can be produced by Ca2+ with substrates such as glutamate, which utilize alpha-ketoglutarate dehydrogenase activity for oxidation. Increases in respiration by Ca2+ may mitigate an increase in ADP during periods of increased

On the temperature effect of substrate and evaporation rate on condensate dispersion

International Nuclear Information System (INIS)

Orlov, Yu.F.; Belotserkovskaya, N.G.; Gustylev, V.K.

1978-01-01

On the basis of available and new experimental data an attempt has been made to generalize the results of studying the effect of the substrate temperature and evaporation rate on the dispersity of amorphous condensates of Sb 2 S 3 and on that of crystalline condensates of PbO and PbTe. The dispersity of the condensates is shown to decrease with a substrate temperature and evaporation rate. The specific surface decreases linearly with the 3-5-fold rise in the evaporation rate. A dispersity decrease is due to the temperature rise in the medium where condensation takes place. The pattern of dispersity dependence on the substrate temperature and evaporation rate does not depend on the mechanism of vapour condensation and is the same both for aerosol mechanism of the condensate formation and for vapour condensation directly on the substrate

Effect of Substrates on the Dynamic Properties of Inkjet-Printed Ag Thin Films

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Deokman Kim

2018-01-01

Full Text Available The dynamic properties of inkjet-printed Ag thin films on flexible substrates were measured using flexural wave propagation. The Ag nanoparticle suspension was inkjet-printed on polyimide (PI, silicon wafer, and glass. The effects of flexible substrates on the dynamic properties of the films were investigated. Beam-shaped Ag-printed substrates were fabricated by pico-second laser pulse cutting. The wave approach was presented to analyze the vibrations of the thin film on the substrates. The Young’s modulus and loss factor of the Ag thin films with the substrates were represented by the combined bending stiffness of the bilayer beam. The vibration response of the base-excited cantilever was measured using an accelerometer and laser Doppler vibrometer (LDV. Vibration transfers were analyzed to obtain dynamic characteristics of the Ag-printed bilayer beam. The substrate affects the reduction of the Ag thin film thickness during the sintering process and surface roughness of the film. The proposed method based on the wave approach allows measurement of the dynamic properties regardless of the ratio of the modulus between the thin film and substrate.

Aldosterone to Active Renin Ratio Is Associated With Nocturnal Blood Pressure in Obese and Treated Hypertensive Patients: The Styrian Hypertension Study

NARCIS (Netherlands)

Grubler, M.R.; Kienreich, K.; Gaksch, M.; Verheyen, N.; Fahrleitner-Pammer, A.; Schmid, J.; Grogorenz, J.; Ablasser, K.; Pieske, B.; Tomaschitz, A.; Pilz, S.

2014-01-01

High aldosterone levels are considered to play a key role in arterial hypertension. Data on the relationship between the aldosterone to active renin ratio (AARR), a quantity of aldosterone excess, and ambulatory blood pressure (BP) monitoring (ABPM) during the night are, however, sparse.

RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

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Zh.P. Sharnova

2006-01-01

Full Text Available To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS in children we determined the genotypes of angiotensin converting enzyme (ACE, angiotensinogen (AGT and angiotensin ii receptor (ATII-R of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF. Genotype frequencies did not differ between patients with ns and controls (n = 165. The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS (n = 18, steroid-sensitive nephrotic syndrome (n = 32, nephrotic syndrome with hypertension and hemoturia (n = 22 and with control group. When ns subjects with CRF (n = 15 were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05. Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05 in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system.

In Situ Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones.

Science.gov (United States)

Takahashi, Kazuhiro; Yatabe, Megumi; Fujiwara, Ken; Hirose, Takuo; Totsune, Kazuhito; Yashiro, Takashi

2013-02-28

Expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, was studied in rat pituitary gland. In situ hybridization showed that cells expressing (P)RR mRNA were widely distributed in the anterior lobe and intermediate lobe of the pituitary gland. Double-staining using in situ hybridization for (P)RR mRNA and immunohistochemistry for the pituitary hormones showed that (P)RR mRNA was expressed in most of the GH cells and ACTH cells in the anterior lobe. (P)RR mRNA was also expressed in a few prolactin cells and TSH cells, but not in LH cells. The present study has shown for the first time the distribution of (P)RR mRNA expressing cells in the rat pituitary gland. These findings suggest that (P)RR plays physiological roles in the pituitary gland, such as the modulation of the pituitary hormone secretion.

In Situ Hybridization Method Reveals (Pro)renin Receptor Expressing Cells in the Pituitary Gland of Rats: Correlation with Anterior Pituitary Hormones

International Nuclear Information System (INIS)

Takahashi, Kazuhiro; Yatabe, Megumi; Fujiwara, Ken; Hirose, Takuo; Totsune, Kazuhito; Yashiro, Takashi

2013-01-01

Expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, was studied in rat pituitary gland. In situ hybridization showed that cells expressing (P)RR mRNA were widely distributed in the anterior lobe and intermediate lobe of the pituitary gland. Double-staining using in situ hybridization for (P)RR mRNA and immunohistochemistry for the pituitary hormones showed that (P)RR mRNA was expressed in most of the GH cells and ACTH cells in the anterior lobe. (P)RR mRNA was also expressed in a few prolactin cells and TSH cells, but not in LH cells. The present study has shown for the first time the distribution of (P)RR mRNA expressing cells in the rat pituitary gland. These findings suggest that (P)RR plays physiological roles in the pituitary gland, such as the modulation of the pituitary hormone secretion

Effect of microneedle geometry and supporting substrate on microneedle array penetration into skin.

Science.gov (United States)

Kochhar, Jaspreet Singh; Quek, Ten Cheer; Soon, Wei Jun; Choi, Jaewoong; Zou, Shui; Kang, Lifeng

2013-11-01

Microneedles are being fast recognized as a useful alternative to injections in delivering drugs, vaccines, and cosmetics transdermally. Owing to skin's inherent elastic properties, microneedles require an optimal geometry for skin penetration. In vitro studies, using rat skin to characterize microneedle penetration in vivo, require substrates with suitable mechanical properties to mimic human skin's subcutaneous tissues. We tested the effect of these two parameters on microneedle penetration. Geometry in terms of center-to-center spacing of needles was investigated for its effect on skin penetration, when placed on substrates of different hardness. Both hard (clay) and soft (polydimethylsiloxane, PDMS) substrates underneath rat skin and full-thickness pig skin were used as animal models and human skins were used as references. It was observed that there was an increase in percentage penetration with an increase in needle spacing. Microneedle penetration with PDMS as a support under stretched rat skin correlated better with that on full-thickness human skin, while penetration observed was higher when clay was used as a substrate. We showed optimal geometries for efficient penetration together with recommendation for a substrate that could better mimic the mechanical properties of human subcutaneous tissues, when using microneedles fabricated from poly(ethylene glycol)-based materials. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effect of substrate type, dopant and thermal treatment on ...

Indian Academy of Sciences (India)

Effect of substrate type, dopant and thermal treatment on physicochemical properties of TiO2–SnO2 sol–gel films. I STAMBOLOVA. ∗. , V BLASKOV, S VASSILEV†, M SHIPOCHKA and A LOUKANOV‡. Institute of General and Inorganic Chemistry, †Institute of Electrochemistry and Energy Systems, BAS,. Acad. G. Bonchev ...

Effects of highly ordered TiO2 nanotube substrates on the nucleation of Cu electrodeposits.

Science.gov (United States)

Ryu, Won Hee; Park, Chan Jin; Kwon, Hyuk Sang

2010-05-01

We investigated the effects of TiO2 nanotube substrates on the nucleation density of Cu during electrodeposition in a solution of CuSO4 and H2SO4 at 50 degrees C compared with those of pure Ti and micro-porous TiO2 substrates. During electrodeposition, the density of Cu nuclei on the TiO2 nanotube substrate increased and the average size of Cu nuclei decreased with increasing anodizing voltage and time for the synthesis of the substrate. In addition, the nucleation density of Cu electrodeposits on the highly ordered TiO2 nanotube substrate was much higher than that on pure Ti and micro-porous TiO2 substrates.

The effect of substrate on thermodynamic and kinetic anisotropies in atomic thin films

International Nuclear Information System (INIS)

Haji-Akbari, Amir; Debenedetti, Pablo G.

2014-01-01

Glasses have a wide range of technological applications. The recent discovery of ultrastable glasses that are obtained by depositing the vapor of a glass-forming liquid onto the surface of a cold substrate has sparked renewed interest in the effects of confinements on physicochemical properties of liquids and glasses. Here, we use molecular dynamics simulations to study the effect of substrate on thin films of a model glass-forming liquid, the Kob-Andersen binary Lennard-Jones system, and compute profiles of several thermodynamic and kinetic properties across the film. We observe that the substrate can induce large oscillations in profiles of thermodynamic properties such as density, composition, and stress, and we establish a correlation between the oscillations in total density and the oscillations in normal stress. We also demonstrate that the kinetic properties of an atomic film can be readily tuned by changing the strength of interactions between the substrate and the liquid. Most notably, we show that a weakly attractive substrate can induce the emergence of a highly mobile region in its vicinity. In this highly mobile region, structural relaxation is several times faster than in the bulk, and the exploration of the potential energy landscape is also more efficient. In the subsurface region near a strongly attractive substrate, however, the dynamics is decelerated and the sampling of the potential energy landscape becomes less efficient than the bulk. We explain these two distinct behaviors by establishing a correlation between the oscillations in kinetic properties and the oscillations in lateral stress. Our findings offer interesting opportunities for designing better substrates for the vapor deposition process or developing alternative procedures for situations where vapor deposition is not feasible

The effect of substrate on thermodynamic and kinetic anisotropies in atomic thin films.

Science.gov (United States)

Haji-Akbari, Amir; Debenedetti, Pablo G

2014-07-14

Glasses have a wide range of technological applications. The recent discovery of ultrastable glasses that are obtained by depositing the vapor of a glass-forming liquid onto the surface of a cold substrate has sparked renewed interest in the effects of confinements on physicochemical properties of liquids and glasses. Here, we use molecular dynamics simulations to study the effect of substrate on thin films of a model glass-forming liquid, the Kob-Andersen binary Lennard-Jones system, and compute profiles of several thermodynamic and kinetic properties across the film. We observe that the substrate can induce large oscillations in profiles of thermodynamic properties such as density, composition, and stress, and we establish a correlation between the oscillations in total density and the oscillations in normal stress. We also demonstrate that the kinetic properties of an atomic film can be readily tuned by changing the strength of interactions between the substrate and the liquid. Most notably, we show that a weakly attractive substrate can induce the emergence of a highly mobile region in its vicinity. In this highly mobile region, structural relaxation is several times faster than in the bulk, and the exploration of the potential energy landscape is also more efficient. In the subsurface region near a strongly attractive substrate, however, the dynamics is decelerated and the sampling of the potential energy landscape becomes less efficient than the bulk. We explain these two distinct behaviors by establishing a correlation between the oscillations in kinetic properties and the oscillations in lateral stress. Our findings offer interesting opportunities for designing better substrates for the vapor deposition process or developing alternative procedures for situations where vapor deposition is not feasible.

The effect of substrate on thermodynamic and kinetic anisotropies in atomic thin films

Energy Technology Data Exchange (ETDEWEB)

Haji-Akbari, Amir; Debenedetti, Pablo G., E-mail: pdebene@exchange.princeton.edu [Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544 (United States)

2014-07-14

Glasses have a wide range of technological applications. The recent discovery of ultrastable glasses that are obtained by depositing the vapor of a glass-forming liquid onto the surface of a cold substrate has sparked renewed interest in the effects of confinements on physicochemical properties of liquids and glasses. Here, we use molecular dynamics simulations to study the effect of substrate on thin films of a model glass-forming liquid, the Kob-Andersen binary Lennard-Jones system, and compute profiles of several thermodynamic and kinetic properties across the film. We observe that the substrate can induce large oscillations in profiles of thermodynamic properties such as density, composition, and stress, and we establish a correlation between the oscillations in total density and the oscillations in normal stress. We also demonstrate that the kinetic properties of an atomic film can be readily tuned by changing the strength of interactions between the substrate and the liquid. Most notably, we show that a weakly attractive substrate can induce the emergence of a highly mobile region in its vicinity. In this highly mobile region, structural relaxation is several times faster than in the bulk, and the exploration of the potential energy landscape is also more efficient. In the subsurface region near a strongly attractive substrate, however, the dynamics is decelerated and the sampling of the potential energy landscape becomes less efficient than the bulk. We explain these two distinct behaviors by establishing a correlation between the oscillations in kinetic properties and the oscillations in lateral stress. Our findings offer interesting opportunities for designing better substrates for the vapor deposition process or developing alternative procedures for situations where vapor deposition is not feasible.

Effect of ipsilateral ureteric obstruction on contralateral kidney and role of renin angiotensin system blockade on renal recovery in experimentally induced unilateral ureteric obstruction

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Shasanka S Panda

2013-01-01

Full Text Available Aims: To study, the effects of ipsilateral ureteric obstruction on contralateral kidney and the role of renin angiotensin system (RAS blockade on renal recovery in experimentally induced unilateral ureteric obstruction. Materials and Methods: Unilateral upper ureteric obstruction was created in 96 adult Wistar rats that were reversed after pre-determined intervals. Losartan and Enalapril were given to different subgroups of rats following relief of obstruction. Results: The severity of dilatation on the contralateral kidney varied with duration of ipsilateral obstruction longer the duration more severe the dilatation. There is direct correlation between renal parenchymal damage, pelvi-ureteric junction (PUJ fibrosis, inflammation and severity of pelvi-calyceal system dilatation of contralateral kidney with duration of ipsilateral PUJ obstruction. Conclusions: Considerable injury is also inflicted to the contralateral normal kidney while ipsilateral kidney remains obstructed. Use of RAS blocking drugs has been found to significantly improve renal recovery on the contralateral kidney. It can, thus, be postulated that contralateral renal parenchymal injury was mediated through activation of RAS.

Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity

DEFF Research Database (Denmark)

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Boomsma, Frans

2009-01-01

hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF...... in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a single-blinded, placebo-controlled, crossover...... study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased...

Involvement of skeletal renin-angiotensin system and kallikrein-kinin system in bone deteriorations of type 1 diabetic mice with estrogen deficiency.

Science.gov (United States)

Zhang, Yan; Wang, Liang; Liu, Jin-Xin; Wang, Xin-Luan; Shi, Qi; Wang, Yong-Jun

This study was aimed to investigate the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal metaphysis. The polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. The mice after treating with ovariectomy and STZ showed the decreased level of serum Ca and the increased level of serum PTH and urine Ca. The H&E staining showed trabecular bone abnormalities as demonstrated by the loss, disconnection and separation of trabecular bone network as well as the loss of chondrocytes and appearance of chondrocyte cluster at growth plate of tibia. The significant increase of matured osteoclast number was shown in group with double treatments. The combination treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor, MMP-9 and CAII, and protein expression of renin, and decreased the ratio of OPG/RANKL and the expression of bradykinin receptors in bone tissue. Ovariectomy combined with STZ induction produced more detrimental actions on bone through the activation of local bone RAS and the down-regulation of bradykinin receptors, as compared to the respective single treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of antihypertensive therapy, sodium intake and the concentration of potassium in plasma on concentration of aldosterone and plasma renin activity

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Lalić Tijana

2013-01-01

Full Text Available Introduction: Primary aldosteronism (PA is a group of disorders which are characterized by inadequate and non-suppressible production of aldosterone. The prevalence of PA is increasing in hypertensive population. The golden standard of screening for primary aldosteronism, determination of aldosterone/plasma renin activity (ARR, is influenced by numerous exogenous and endogenous factors. Testing cannot always be conducted under optimal conditions. Objective: To determine influence of antihypertensive drugs and concentrations of potassium and sodium in blood and urine on values of aldosterone and plasma renin activity. Methods: In this retrospective study, we analyzed medical reports of patients admitted to Department of thyroid gland disease in the period from 2009 to 2011, with increased risk for primary aldosteronism. Body weight and height, sodium and potassium in serum and urine, plasma aldosterone concentrations and plasma renin activity, data on medicines and comorbidity were analyzed in all patients. In processing data, statistical methods descriptive analysis, Student T test and univariate linear regression were applied. Result: Of 137 patients, there were more patients with resistant hypertension (53,28% than with adrenal tumors (46,72%. Most patients used calcium channel blockers. Treatment with alpha blockers and calcium channel blockers does not influence ARR. Beta blockers and ACE inhibitors can influence ARR and diuretics and vasodilatators have definite influence. Diabetes mellitus can have higher risk of false negative results. Urine sodium excretion is significantly correlated with plasma aldosteron and serum potassium. Plasma aldosteron and PRA are significantly correlated with concentrations of electrolites in urine. Conclusion: Increased prevalence of primary aldosteronism necessitates need for accurate and better diagnostics.

Effect of the Direct Renin Inhibitor Aliskiren on Urinary Albumin Excretion in Spontaneous Type 2 Diabetic KK-A y Mouse

Science.gov (United States)

Furukawa, Masako; Horikoshi, Satoshi; Funabiki, Kazuhiko; Tomino, Yasuhiko

2013-01-01

Objective. Although angiotensin II-mediated inflammation and extracellular matrix accumulation are considered to be associated with the progression of diabetic nephropathy, these processes have not yet been sufficiently clarified. The objective of this study was to determine whether the correction of the abnormal renal expression of MMPs and its inhibitors (MMPs/TIMPs) and cytokines following the administration of aliskiren to KK-A y mice results in a renoprotective effect. Methods. KK-A y mice were divided into two groups, that is, untreated (saline) and treated (aliskiren) groups. Systolic BP, HbA1c levels, and the albumin-creatinine ratio (ACR) were measured. The renal expression of MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (pro)renin receptor ((P)RR) was examined using real-time PCR and/or immunohistochemical staining. Renal MAPK and NF-κB activity were also examined by Western blot analyses and ELISA, respectively. Results. Significant decreases in systolic BP and ACR levels were observed in treated KK-A y mice compared with the findings in untreated KK-A y mice. Furthermore, increases in MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (P)RR expression, in addition to MAPK and NF-κB activity, were significantly attenuated by aliskiren administration. Conclusions. It appears that aliskiren improves albuminuria and renal fibrosis by regulating inflammation and the alteration of collagen synthesis and degradation. PMID:23819050

A signal-substrate match in the substrate-borne component of a multimodal courtship display

Directory of Open Access Journals (Sweden)

Damian O. ELIAS, Andrew C. MASON, Eileen A. HEBETS

2010-06-01

Full Text Available The environment can impose strong limitations on the efficacy of signal transmission. In particular, for vibratory communication, the signaling environment is often extremely heterogeneous at very small scales. Nevertheless, natural selection is expected to select for signals well-suited to effective transmission. Here, we test for substrate-dependent signal efficacy in the wolf spider Schizocosa stridulans Stratton 1991. We first explore the transmission characteristics of this important signaling modality by playing recorded substrate-borne signals through three different substrates (leaf litter, pine litter, and red clay and measuring the propagated signal. We found that the substrate-borne signal of S. stridulans attenuates the least on leaf litter, the substrate upon which the species is naturally found. Next, by assessing mating success with artificially muted and non-muted males across different signaling substrates (leaf litter, pine litter, and sand, we explored the relationship between substrate-borne signaling and substrate for mating success. We found that muted males were unsuccessful in obtaining copulations regardless of substrate, while mating success was dependent on the signaling substrate for non-muted males. For non-muted males, more males copulated on leaf litter than any other substrate. Taken together, these results confirm the importance of substrate-borne signaling in S. stridulans and suggest a match between signal properties and signal efficacy – leaf litter transmits the signal most effectively and males are most successful in obtaining copulations on leaf litter [Current Zoology 56 (3: 370–378, 2010].

Combining Solvent Isotope Effects with Substrate Isotope Effects in Mechanistic Studies of Alcohol and Amine Oxidation by Enzymes*

Science.gov (United States)

Fitzpatrick, Paul F.

2014-01-01

Oxidation of alcohols and amines is catalyzed by multiple families of flavin-and pyridine nucleotide-dependent enzymes. Measurement of solvent isotope effects provides a unique mechanistic probe of the timing of the cleavage of the OH and NH bonds, necessary information for a complete description of the catalytic mechanism. The inherent ambiguities in interpretation of solvent isotope effects can be significantly decreased if isotope effects arising from isotopically labeled substrates are measured in combination with solvent isotope effects. The application of combined solvent and substrate (mainly deuterium) isotope effects to multiple enzymes is described here to illustrate the range of mechanistic insights that such an approach can provide. PMID:25448013

Green roofs for a drier world: effects of hydrogel amendment on substrate and plant water status.

Science.gov (United States)

Savi, Tadeja; Marin, Maria; Boldrin, David; Incerti, Guido; Andri, Sergio; Nardini, Andrea

2014-08-15

Climate features of the Mediterranean area make plant survival over green roofs challenging, thus calling for research work to improve water holding capacities of green roof systems. We assessed the effects of polymer hydrogel amendment on the water holding capacity of a green roof substrate, as well as on water status and growth of Salvia officinalis. Plants were grown in green roof experimental modules containing 8 cm or 12 cm deep substrate (control) or substrate mixed with hydrogel at two different concentrations: 0.3 or 0.6%. Hydrogel significantly increased the substrate's water content at saturation, as well as water available to vegetation. Plants grown in 8 cm deep substrate mixed with 0.6% of hydrogel showed the best performance in terms of water status and membrane integrity under drought stress, associated to the lowest above-ground biomass. Our results provide experimental evidence that polymer hydrogel amendments enhance water supply to vegetation at the establishment phase of a green roof. In particular, the water status of plants is most effectively improved when reduced substrate depths are used to limit the biomass accumulation during early growth stages. A significant loss of water holding capacity of substrate-hydrogel blends was observed after 5 months from establishment of the experimental modules. We suggest that cross-optimization of physical-chemical characteristics of hydrogels and green roof substrates is needed to improve long term effectiveness of polymer-hydrogel blends. Copyright © 2014 Elsevier B.V. All rights reserved.

EFFECT OF USING VARIOUS SUBSTRATES ON CULTIVATION OF PLEUROTUS SAJOR-CAJU

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S. N. FASEHAH

2017-04-01

Full Text Available The unmanageable agricultural waste comprises of structural polymers, cellulose, hemicellulose and lignin can be led to pollutions, thus it can be used as a mushroom substrate. Lignocellulosic materials are most favorable feedstock as renewable and natural resource. Forestry and agricultural practices generated a large amount of ligncelluosic waste and promoted to serious problematic environmental pollution. It can be easily broken down by lignocellulotic enzymes. In this study, an attempt was made to evaluate the effect of various substrates on cultivation of Pleurotus sajor-caju. The substrates used in this study were tissue paper, rice husk ash and rubber sawdust. All of the substrates were added with rice bran and calcium carbonate (CaCO3. Then, the mixtures were transferred into plastic sized 8 cm × 4.5 cm and were pasteurized in the steamer for 1 hour at60 °C - 100 °C. After that they were cooled overnight at 25 °C - 30 °C. The spawn were inoculated into the bag and incubated in incubation room. The media bags were incubated until mycelium fully colonized and watering was done twice a day. The parameters studies were included spawn running, number of fruit body, total of stipe length, weight of fruit body and biological efficiency. Results showed that the fastest spawn running and highest number of fruits body, total of stipe length, weight of fruit body and biological efficiency are found using tissue paper substrates. In contrast the rubber sawdust showed the lowest values of spawn running, total of stipe length, weight of fruit body and biological efficiency. It can be concluded that the tissue paper is one of promising substrate which can be used in growing of Pleurotus sajor-caju due to lower cost and easy to purchase as compared to other substrates.

Effects of sulfamethoxazole on soil microbial communities after adding substrate.

NARCIS (Netherlands)

Demoling, L.A.; Baath, E.; Greve, G.D.; Wouterse, M.; Schmitt, H.

2009-01-01

The effect of the antibiotic sulfamethoxazole (SMX) on soil bacteria was studied using two methods (leucine incorporation and Biolog plates) of estimating pollution-induced community tolerance (PICT). SMX was added to an agricultural soil in a microcosm setup. The addition of different substrates

Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

Science.gov (United States)

O'Malley, K; Velasco, M; Wells, J; McNay, J L

1975-01-01

A study was made of the possible mechanism(s) underlying minoxidil-induced increase in plasma renin activity (PRA). 10 patients with essential hypertension were treated with minoxidil and subsequently with a combination of minoxidil plus propranolol. Minoxidil lowered mean arterial pressure 31.6 plus or minus 3.3 mm Hg, mean plus or minus SEM. There was an associated increase in both PRA, 6.26 plus or minus 2.43 NG/ML/H, and heart rate, 21.4 plus or minus 2.7 beats/min. The changes in PRA and heart rate were positively correlated, r, 0.79. Addition of propranolol reduced mean arterial pressure by a further 10.1 plus or minus 1.5 mm Hg and returned heart rate to control levels. Propranolol reduced PRA significantly but not to control levels. Control PRA positively correlated with PRA on minoxidil, r, 0.97, and with PRA on minoxidil plus propranolol, r, 0.98. We conclude that control PRA is a major determinant of change in PRA with minoxidil. Minoxidil increased PRA by at least two mechanisms: (a) an adrenergic mechanism closely related to change in heart rate and blocked by propranolol, and (b) a mechanism(s) not sensitive to propranolol and possibly related to decrease in renal perfusion pressure. PMID:1127099

Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

OpenAIRE

Renna, N. F.; Lembo, C.; Diez, E.; Miatello, R. M.

2013-01-01

(1) is study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular inammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10−3 mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and systo...

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

Effect of modification substrate on the microstructure of hydroxyapatite coating

International Nuclear Information System (INIS)

Realpe-Jaramillo, J; Morales-Morales, J A; González-Sánchez, J A; Cabanzo, R; Mejía-Ospino, E; Rodríguez-Pereira, J

2017-01-01

Bioactive hydroxyapatite (HA) coatings were fabricated by a precipitation, sol-gel and dip-coating method. The effects of the aging time and the base used to adjust pH and substrate materials on the phases and microstructures of HA coatings were studied by field emission scanning electron microscopy FESEM, energy dispersive spectroscopy EDS, X-ray photoelectron spectroscopy XPS, and the vibrations of the phosphate groups were determined by Raman spectroscopy. The results showed that all the films were composed of the phases of TiO 2 and HA. With coated titanium substrate with TiO 2 , the crystallinity of the HA coating increases, the structure became more compact and the Ca/P ratio increased because of the loss of P in the films. The addition of sodium hydroxide (adjusting the pH level to about 10) can increase the HA content in the coating. XPS and EDS results for steel substrate and titanium showed poor calcium content as obtained with a Ca/P ratio of 1.38 and 1.58, respectively, composition is similar to that of natural apatite. However, spectroscopic results suggest the presence of a mixture of hydroxyapatite and octacalcium phosphate. The different substrate materials have a high influence on the microstructure of the separated double films. However, hydroxyapatite nanopowders coatings were obtained using a simple method, with potential biomedical applications. (paper)

Effect of modification substrate on the microstructure of hydroxyapatite coating

Science.gov (United States)

Realpe-Jaramillo, J.; Morales-Morales, J. A.; González-Sánchez, J. A.; Cabanzo, R.; Mejía-Ospino, E.; Rodríguez-Pereira, J.

2017-01-01

Bioactive hydroxyapatite (HA) coatings were fabricated by a precipitation, sol-gel and dip-coating method. The effects of the aging time and the base used to adjust pH and substrate materials on the phases and microstructures of HA coatings were studied by field emission scanning electron microscopy FESEM, energy dispersive spectroscopy EDS, X-ray photoelectron spectroscopy XPS, and the vibrations of the phosphate groups were determined by Raman spectroscopy. The results showed that all the films were composed of the phases of TiO2 and HA. With coated titanium substrate with TiO2, the crystallinity of the HA coating increases, the structure became more compact and the Ca/P ratio increased because of the loss of P in the films. The addition of sodium hydroxide (adjusting the pH level to about 10) can increase the HA content in the coating. XPS and EDS results for steel substrate and titanium showed poor calcium content as obtained with a Ca/P ratio of 1.38 and 1.58, respectively, composition is similar to that of natural apatite. However, spectroscopic results suggest the presence of a mixture of hydroxyapatite and octacalcium phosphate. The different substrate materials have a high influence on the microstructure of the separated double films. However, hydroxyapatite nanopowders coatings were obtained using a simple method, with potential biomedical applications.

Effects of gender on screening value of aldosterone-renin ratio for primary aldosteronism

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Ye-qiong SONG

2017-02-01

Full Text Available Objective　To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR for primary aldosteronism (PA. Methods　The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC was conducted to evaluate the best cut-off value. Results　The plasma aldosterone concentration (PAC, serum sodium and ARR were much higher, but the plasma rennin activity (PRA, serum potassium and BMI were much lower in PA patients than in EH patients (P0.05. The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC was 0.968, the sensitivity and specificity was 92.44% and 93.08%, and the Youden index (YI was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specificity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specificity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specificity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the official value recommended by guidelines. Conclusion　Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher. DOI: 10.11855/j.issn.0577-7402.2017.01.10

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity

DEFF Research Database (Denmark)

Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due

2009-01-01

INTRODUCTION: High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patient...

Effect of Nanosilica Filled Polyurethane Composite Coating on Polypropylene Substrate

Directory of Open Access Journals (Sweden)

Yern Chee Ching

2013-01-01

Full Text Available Acrylic based polyurethane (PU coatings with various amounts of nanosilica contents were prepared using solution casting method. The nanosilica (SiO2 particles used are around 16 nm in diameter. The friction and wear test was conducted using the reciprocating wear testing machine. The tests were performed at rotary speed of 100 rpm and 200 rpm with load of 0.1 kg to 0.4 kg under 1 N interval. The effect of the PU/nano-SiO2 composite coating on friction and wear behavior of polypropylene substrate was investigated and compared. The worn surface of coating film layer after testing was investigated by using an optical microscope. The introduction of PU/nanosilica composite coating containing 3 wt% of nano-SiO2 content gives the lowest friction coefficient and wear rate to PP substrate. Both the friction and wear rate of PP substrate coated with >3 wt% of nano-SiO2 filled PU coating would increase with the increasing of applied load and sliding time.

Proteolytic Activity of Prostate-Specific Antigen (PSA) towards Protein Substrates and Effect of Peptides Stimulating PSA Activity

Science.gov (United States)

Mattsson, Johanna M.; Ravela, Suvi; Hekim, Can; Jonsson, Magnus; Malm, Johan; Närvänen, Ale; Stenman, Ulf-Håkan; Koistinen, Hannu

2014-01-01

Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3) exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA. PMID:25237904

Effects of substrate temperature, substrate orientation, and energetic atomic collisions on the structure of GaN films grown by reactive sputtering

Energy Technology Data Exchange (ETDEWEB)

Schiaber, Ziani S.; Lisboa-Filho, Paulo N.; Silva, José H. D. da [Universidade Estadual Paulista, UNESP, Bauru, São Paulo 17033-360 (Brazil); Leite, Douglas M. G. [Universidade Federal de Itajubá, UNIFEI, Itajubá, Minas Gerais 37500-903 (Brazil); Bortoleto, José R. R. [Universidade Estadual Paulista, UNESP, Sorocaba, São Paulo 18087-180 (Brazil)

2013-11-14

The combined effects of substrate temperature, substrate orientation, and energetic particle impingement on the structure of GaN films grown by reactive radio-frequency magnetron sputtering are investigated. Monte-Carlo based simulations are employed to analyze the energies of the species generated in the plasma and colliding with the growing surface. Polycrystalline films grown at temperatures ranging from 500 to 1000 °C clearly showed a dependence of orientation texture and surface morphology on substrate orientation (c- and a-plane sapphire) in which the (0001) GaN planes were parallel to the substrate surface. A large increase in interplanar spacing associated with the increase in both a- and c-parameters of the hexagonal lattice and a redshift of the optical bandgap were observed at substrate temperatures higher than 600 °C. The results showed that the tensile stresses produced during the film's growth in high-temperature deposition ranges were much larger than the expected compressive stresses caused by the difference in the thermal expansion coefficients of the film and substrate in the cool-down process after the film growth. The best films were deposited at 500 °C, 30 W and 600 °C, 45 W, which corresponds to conditions where the out diffusion from the film is low. Under these conditions the benefits of the temperature increase because of the decrease in defect density are greater than the problems caused by the strongly strained lattice that occurr at higher temperatures. The results are useful to the analysis of the growth conditions of GaN films by reactive sputtering.

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial.

Science.gov (United States)

de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

2016-06-01

In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. Two-center randomized crossover trial. Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-sodium diet to 87±55mmol/24 h during the low-sodium diet (mean difference, -77 [95% CI, -110 to -44] mmol/24 h; Padherence to sodium diet was achieved in 86% of patients. In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effect of the substrate orientation on the formation of He-plates in Si

International Nuclear Information System (INIS)

Vallet, M.; Barbot, J. F.; Declémy, A.; Beaufort, M. F.; Reboh, S.

2013-01-01

The effect of the crystalline orientation on the implantation-induced strain/stress and on the formation of He-plates was studied by combining high-resolution X-ray scattering and transmission electron microscopy. The highest strains are obtained in (001)-oriented implanted substrates regardless of the fluence and of the channeling effects. The anisotropic properties of the silicon that generate an anisotropic elastic response of the substrate were taken into account to explain these different values of strain. Upon specific thermal annealing, it is shown that the formation of He-plates occurs only in the (001) habit planes regardless of the orientation of the substrates, non-tilted and tilted (001)-, (110)-, and (111)-substrates. Moreover, the distribution of He-plates in the (001) variants was found to be strongly dependent on the angle of the habit plane with the surface and on the intensity of the implantation-induced strain/stress. The implantation-induced stress thus favors the formation of He-plates in specific planes (of low angle with the surface) forming different defect configurations. The nucleation and growth of He-plates are thus discussed with regard to the implantation-induced stress

Renin angiotensin system and gender differences in dopaminergic degeneration

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Rodriguez-Perez Ana I

2011-08-01

Full Text Available Abstract Background There are sex differences in dopaminergic degeneration. Men are approximately two times as likely as premenopausal women of the same age to develop Parkinson's disease (PD. It has been shown that the local renin angiotensin system (RAS plays a prominent role in sex differences in the development of chronic renal and cardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin via type 1 (AT1 receptors. Results In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked loss of dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss induced in ovariectomized female rats given estrogen implants (i.e. rats with estrogen. However, the loss of dopaminergic neurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to that observed in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergic degeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantly higher expression of AT1 receptors, angiotensin converting enzyme activity, and NADPH-oxidase complex activity, and much lower levels of AT2 receptors were observed in male rats than in female rats with estrogen. Conclusions The results suggest that brain RAS plays a major role in the increased risk of developing PD in men, and that manipulation of brain RAS may be an efficient approach for neuroprotective treatment of PD in men, without the feminizing effects of estrogen.

Effect of sweet pepper cultivation on the content of phytotoxic phenolic compounds in substrates

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Barbara Politycka

2013-12-01

Full Text Available The aim of the conducted study was to determine to what extent the cultivation of sweet pepper lowers the phytotoxicity of a substrate. The examined material was a highly phytotoxic substrate due to repeated cucumber growing on it. This substrate was a mixture of pine and beech bark, low peat and sawdust. Five sweet pepper cultivars: Amador, Bell Boy, Culinar, Poznańska Słodka and WSE 2/82 were planted. During vegetation of the sweet pepper phytotoxicity and phenolics levels were determined in the substrate. It was found that cultivation of sweet pepper had a significant effect on lowering phytotoxicity and phenolics content in the substrate. Among the five tested cultivars, the highest detoxicating ability was exhibited by Amador, Culinar and WSE 2/82 while the Poznańska Słodka did not show such abilities.

Effect of substrate properties and thermal annealing on the resistivity of molybdenum thin films

International Nuclear Information System (INIS)

Schmid, U.; Seidel, H.

2005-01-01

In this study, the influence of substrate properties (e.g. roughness characteristics and chemical composition) on the electrical resistivity of evaporated molybdenum thin films is investigated as a function of varying parameters, such as film thickness (25-115 nm) and post-deposition annealing with temperatures up to T PDA = 900 deg. C. A thermally oxidized silicon wafer with very low surface roughness was used as one substrate type. In contrast, a low temperature co-fired ceramics substrate with a glass encapsulant printed in thick film technology is the representative for rough surface morphology. The electrical resistivity follows the prediction of the size effect up to T PDA = 600 deg. C independent of substrate nature. On the silicon-based substrate, the thickness-independent portion of the film resistivity ρ g in the 'as deposited' state is about 29 times higher than the corresponding bulk value for a mono-crystalline sample. Thin films of this refractory metal on the SiO 2 /Si substrate exhibit an average grain size of 4.9 nm and a negative temperature coefficient of resistivity (TCR). On the glass/ceramic-based substrate, however, ρ g is half the value as compared to that obtained on the SiO 2 /Si substrate and the TCR is positive

The influence of a tilt training programme on the renin-angiotensin-aldosterone system activity in patients with vasovagal syncope.

Science.gov (United States)

Gajek, Jacek; Zyśko, Dorota; Krzemińska, Sylwia; Mazurek, Walentyna

2009-08-01

We assessed the influence of short-term and long-term tilt training on the activity of the renin-angiotensin-aldosterone system (RAAS) in vasovagal patients. Thirty-nine patients (28 F, 11 M) aged 39.7 +/- 11.2 years with a history of vasovagal syncope and a positive head-up tilt test (HUT) were studied. Blood samples for plasma renin activity (PRA) and aldosterone (ALDO) concentration were drawn at the baseline, immediately after HUT and 10 min after HUT, during the diagnostic, the negative short-term (2-5 days) follow-up HUT and long-term (1-3 months) follow-up HUT. Tilt training was started after diagnostic HUT. In diagnostic HUT, PRA increased significantly immediately after HUT comparing to the baseline, during recovery the values did not change. ALDO concentration increased after HUT comparing to baseline and further increased during recovery. After short-term tilt training, PRA and ALDO concentrations did not significantly change compared to their corresponding values in diagnostic HUT. After long-term tilt training, PRA did not significantly change compared to the values in the diagnostic and short-term follow-up HUT. ALDO concentration also did not change significantly at the baseline and immediately after HUT, and 10 min after HUT ALDO concentration was significantly lower than after diagnostic HUT. Tilt training changes the response of RAAS to the prolonged orthostasis in vasovagal patients. The coupling between PRA and ALDO after diagnostic HUT has been found to be altered and the physiological relationship was restored after long-term tilt training. The beneficial effect of tilt training depends partially on changed RAAS activation.

Surface treatment effect on Si (111) substrate for carbon deposition using DC unbalanced magnetron sputtering

Energy Technology Data Exchange (ETDEWEB)

Aji, A. S., E-mail: aji.ravazes70@gmail.com; Sahdan, M. F.; Hendra, I. B.; Dinari, P.; Darma, Y. [Quantum Semiconductor and Devices Lab., Physics of Material Electronics Research Division, Department of Physics, Institut Teknologi Bandung (Indonesia)

2015-04-16

In this work, we studied the effect of HF treatment in silicon (111) substrate surface for depositing thin layer carbon. We performed the deposition of carbon by using DC Unbalanced Magnetron Sputtering with carbon pallet (5% Fe) as target. From SEM characterization results it can be concluded that the carbon layer on HF treated substrate is more uniform than on substrate without treated. Carbon deposition rate is higher as confirmed by AFM results if the silicon substrate is treated by HF solution. EDAX characterization results tell that silicon (111) substrate with HF treatment have more carbon fraction than substrate without treatment. These results confirmed that HF treatment on silicon Si (111) substrates could enhance the carbon deposition by using DC sputtering. Afterward, the carbon atomic arrangement on silicon (111) surface is studied by performing thermal annealing process to 900 °C. From Raman spectroscopy results, thin film carbon is not changing until 600 °C thermal budged. But, when temperature increase to 900 °C, thin film carbon is starting to diffuse to silicon (111) substrates.

Electronic, structural, and substrate effect properties of single-layer covalent organic frameworks

International Nuclear Information System (INIS)

Liang, Liangbo; Zhu, Pan; Meunier, Vincent

2015-01-01

Recently synthesized two-dimensional covalent organic frameworks (COFs) exhibit high surface area, large pore size, and unique structural architectures, making them promising materials for various energy applications. Here, a total of nine COFs structures, including two deposited on a hexagonal boron nitride substrate, are investigated using density functional theory, quasi-particle many-body theory within the GW approximation, and an image charge model. The structures considered belong to two major families (thiophene-based COF-n (T-COF-n) and tetrakis (4-aminophenyl) porphyrin-x (TAPP-x)) differing from the presence of B—O or C=N linkers. While T-COF-n structures are shown to constitute planar networks, TAPP-x systems can display non-negligible corrugation due to the out-of-plane rotation of phenyl rings. We find that the electronic properties do not differ significantly when altering the chain molecules within each family. Many-body effects are shown to lead to large band-gap increase while the presence of the substrate yields appreciable reductions of the gaps, due to substrate polarization effects

Free Fatty Acids Activate Renin-Angiotensin System in 3T3-L1 Adipocytes through Nuclear Factor-kappa B Pathway

Directory of Open Access Journals (Sweden)

Jia Sun

2016-01-01

Full Text Available The activity of a local renin-angiotensin system (RAS in the adipose tissue is closely associated with obesity-related diseases. However, the mechanism of RAS activation in adipose tissue is still unknown. In the current study, we found that palmitic acid (PA, one kind of free fatty acid, induced the activity of RAS in 3T3-L1 adipocytes. In the presence of fetuin A (Fet A, PA upregulated the expression of angiotensinogen (AGT and angiotensin type 1 receptor (AT1R and stimulated the secretion of angiotensin II (ANG II in 3T3-L1 adipocytes. Moreover, the activation of RAS in 3T3-L1 adipocytes was blocked when we blocked Toll-like receptor 4 (TLR4 signaling pathway using TAK242 or NF-κB signaling pathway using BAY117082. Together, our results have identified critical molecular mechanisms linking PA/TLR4/NF-κB signaling pathway to the activity of the local renin-angiotensin system in adipose tissue.

Microscopic theory of substrate-induced gap effect on real AFM ...

Indian Academy of Sciences (India)

2017-06-24

Jun 24, 2017 ... We address here a tight-binding model study of frequency-dependent real part of antiferromagnetic susceptibility for the graphene systems. TheHamiltonian consists of electron hopping upto third nearest-neighbours,substrate and impurity effects in the presence of electron–electron interactions at A and B ...

Effects O2 plasma surface treatment on the electrical properties of the ITO substrate

International Nuclear Information System (INIS)

Hong, Jin-Woong; Oh, Dong-Hoon; Shim, Sang-Min; Lee, Young-Sang; Kang, Yong-Gil; Shin, Jong-Yeol

2012-01-01

The indium-tin-oxide (ITO) substrate is used as a transparent electrode in organic light-emitting diodes (OLEDs) and organic photovoltaic cells. The effect of an O 2 plasma surface treatment on the electrical properties of the ITO substrate was examined. The four-point probe method, an atomic force microscope (AFM), a LCR meter, a Cole-Cole plot, and a conductive mechanism analysis were used to assess the properties of the treated ITO substrates. The four-point probe method and the AFM study revealed a lower ITO surface resistance of 17.6 Ω/sq and an average roughness of 2 nm, respectively, for a substrate treated by a plasma at 250 W for 40 s. The lower surface resistance of the ITO substrate treated at 250 W for 40 s was confirmed by using a LCR meter. An amorphous fluoropolymer (AF) was deposited on an ITO substrate treated under the optimal conditions and on a non-plasma treated ITO substrate as well. The potential barriers for charge injection in these devices were 0.25 eV and 0.15 eV, respectively, indicating a 0.1-eV decrease due to the plasma treatment.

Brain renin angiotensin system in cardiac hypertrophy and failure

Directory of Open Access Journals (Sweden)

Luciana eCampos

2012-01-01

Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

Proteolytic activity of prostate-specific antigen (PSA towards protein substrates and effect of peptides stimulating PSA activity.

Directory of Open Access Journals (Sweden)

Johanna M Mattsson

Full Text Available Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3 exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA.

Addition of ETA receptor blockade increases renoprotection provided by renin-angiotensin system blockade in 5/6 nephrectomized Ren-2 transgenic rats

Czech Academy of Sciences Publication Activity Database

Čertíková; Chábová, V.; Vernerová, Z.; Kujal, P.; Husková, Z.; Škaroupková, P.; Tesař, V.; Kramer, H. J.; Kompanowska; Jezierska, E.; Walkowska, A.; Sadowski, J.; Červenka, L.; Vaněčková, Ivana

2014-01-01

Roč. 118, č. 2 (2014), s. 297-305 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : renal failure * 5/6 nephrectomy * renin-angiotensin * endothelin * survival Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.702, year: 2014

The renin-angiotensin-aldosterone system (RAAS – physiology and molecular mechanisms of functioning

Directory of Open Access Journals (Sweden)

Monika Chaszczewska-Markowska

2016-09-01

Full Text Available Secretion of renin juxtaglomerular cells into bloodstream initiates activation of an enzymatic-hormonal cascade known as the RAAS (renin – angiotensin – aldosterone system. As a result, blood pressure is increased by the means several interrelated mechanisms. Mechanism of Zjednoczoaction of this system has been known for decades, but a few previously unknown components were recently added, such as ACE-2 and Ang(1-7, and their role often seems to be opposite to that of the conventional components. Local tissue systems also have important biological functions. They operate largely independently of the systemic activity, and their activity is observed primarily in the kidney, heart, in blood vessels, adrenal gland and nervous system. Angiotensin-2 (Ang-2, the main RAAS effector, has a wide scope of action, and thus abnormalities in its functioning have many consequences. Excessive activation is accompanied by chronic inflammation, as Ang-2 stimulates inflammatory mediators. As a result, degenerative processes and atherosclerosis are initiated. RAAS imbalance is associated with the most common diseases of civilization, such as cardio-vascular diseases, diabetes, kidney diseases, preeclampsia, osteoporosis and even neurodegenerative diseases. Many of these pathological processes are attributed to the excessive activation of tissue RA system. Therapeutic strategies based on inhibition of the RAAS are commonly used mainly in the treatment of hypertension and other cardiovascular disorders. The benefits of this class of drugs is primarily a decrease in blood pressure, but also the suppression of inflammatory processes and other pathological phenomena resulting from excessive activation of the RAAS. For that reason, some consider to use RAAS inhibitors in other diseases, e.g. Parkinson’s disease. Further studies give hope for the improvement of RAAS inhibitor therapy and the development of new therapeutic strategies

Silicon nanowire-based tunneling field-effect transistors on flexible plastic substrates.

Science.gov (United States)

Lee, Myeongwon; Koo, Jamin; Chung, Eun-Ae; Jeong, Dong-Young; Koo, Yong-Seo; Kim, Sangsig

2009-11-11

A technique to implement silicon nanowire (SiNW)-based tunneling field-effect transistors (TFETs) on flexible plastic substrates is developed for the first time. The p-i-n configured Si NWs are obtained from an Si wafer using a conventional top-down CMOS-compatible technology, and they are then transferred onto the plastic substrate. Based on gate-controlled band-to-band tunneling (BTBT) as their working principle, the SiNW-based TFETs show normal p-channel switching behavior with a threshold voltage of -1.86 V and a subthreshold swing of 827 mV/dec. In addition, ambipolar conduction is observed due to the presence of the BTBT between the heavily doped p+ drain and n+ channel regions, indicating that our TFETs can operate in the n-channel mode as well. Furthermore, the BTBT generation rates for both the p-channel and n-channel operating modes are nearly independent of the bending state (strain = 0.8%) of the plastic substrate.

Silicon nanowire-based tunneling field-effect transistors on flexible plastic substrates

International Nuclear Information System (INIS)

Lee, Myeongwon; Koo, Jamin; Chung, Eun-Ae; Jeong, Dong-Young; Kim, Sangsig; Koo, Yong-Seo

2009-01-01

A technique to implement silicon nanowire (SiNW)-based tunneling field-effect transistors (TFETs) on flexible plastic substrates is developed for the first time. The p-i-n configured Si NWs are obtained from an Si wafer using a conventional top-down CMOS-compatible technology, and they are then transferred onto the plastic substrate. Based on gate-controlled band-to-band tunneling (BTBT) as their working principle, the SiNW-based TFETs show normal p-channel switching behavior with a threshold voltage of -1.86 V and a subthreshold swing of 827 mV/dec. In addition, ambipolar conduction is observed due to the presence of the BTBT between the heavily doped p + drain and n + channel regions, indicating that our TFETs can operate in the n-channel mode as well. Furthermore, the BTBT generation rates for both the p-channel and n-channel operating modes are nearly independent of the bending state (strain = 0.8%) of the plastic substrate.

Silicon nanowire-based tunneling field-effect transistors on flexible plastic substrates

Energy Technology Data Exchange (ETDEWEB)

Lee, Myeongwon; Koo, Jamin; Chung, Eun-Ae; Jeong, Dong-Young; Kim, Sangsig [Department of Electrical Engineering and Institute for Nano Science, Korea University, 5-1, Anam-Dong, Seongbuk-Gu, Seoul 136-701 (Korea, Republic of); Koo, Yong-Seo, E-mail: sangsig@korea.ac.k [Department of Electrical Engineering, Seokyeong University, 16-1, Jungneung-dong, Seongbuk-gu, Seoul 136-704 (Korea, Republic of)

2009-11-11

A technique to implement silicon nanowire (SiNW)-based tunneling field-effect transistors (TFETs) on flexible plastic substrates is developed for the first time. The p-i-n configured Si NWs are obtained from an Si wafer using a conventional top-down CMOS-compatible technology, and they are then transferred onto the plastic substrate. Based on gate-controlled band-to-band tunneling (BTBT) as their working principle, the SiNW-based TFETs show normal p-channel switching behavior with a threshold voltage of -1.86 V and a subthreshold swing of 827 mV/dec. In addition, ambipolar conduction is observed due to the presence of the BTBT between the heavily doped p{sup +} drain and n{sup +} channel regions, indicating that our TFETs can operate in the n-channel mode as well. Furthermore, the BTBT generation rates for both the p-channel and n-channel operating modes are nearly independent of the bending state (strain = 0.8%) of the plastic substrate.

Synergistic effect of cellulase and xylanase during hydrolysis of natural lignocellulosic substrates.

Science.gov (United States)

Song, Hui-Ting; Gao, Yuan; Yang, Yi-Min; Xiao, Wen-Jing; Liu, Shi-Hui; Xia, Wu-Cheng; Liu, Zi-Lu; Yi, Li; Jiang, Zheng-Bing

2016-11-01

Synergistic combination of cellulase and xylanase has been performed on pre-treated substrates in many previous studies, while few on natural substrates. In this study, three unpretreated lignocellulosic substrates were studied, including corncob, corn stover, and rice straw. The results indicated that when the mixed cellulase and xylanase were applied, reducing sugar concentrations were calculated as 19.53, 15.56, and 17.35mg/ml, respectively, based on the 3,5 dinitrosalicylic acid (DNS) method. Compared to the treatment with only cellulose, the hydrolysis yields caused by mixed cellulase and xylanase were improved by 133%, 164%, and 545%, respectively. In addition, the conversion yield of corncob, corn stover, and rice straw by cellulase-xylanase co-treatment reached 43.9%, 48.5%, and 40.2%, respectively, based on HPLC analysis, which confirmed the synergistic effect of cellulase-xylanase that was much higher than either of the single enzyme treatment. The substrate morphology was also evaluated to explore the synergistic mechanism of cellulase-xylanase. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ratchet Effects, Negative Mobility, and Phase Locking for Skyrmions on Periodic Substrates

Science.gov (United States)

Reichhardt, Charles; Ray, Dipanjan; Olson Reichhardt, Cynthia

We examine the dynamics of skyrmions interacting with 1D and 2D periodic substrates in the presence of dc and ac drives. We find that the Magnus term strongly affects the skyrmion dynamics and that new kinds of phenomena can occur which are absent for overdamped ac and dc driven particles interacting with similar substrates. We show that it is possible to realize a Magnus induced ratchet for skyrmions interacting with an asymmetric potential, where the application of an ac drive can produce quantized dc motion of the skyrmions even when the ac force is perpendicular to the substrate asymmetry direction. For symmetric substrates it is also possible to achieve a negative mobility effect where the net skyrmion motion runs counter to an applied dc drive. Here, as a function of increasing dc drive, the velocity-force curves show a series of locking phases that have different features from the classic Shapiro steps found in overdamped systems. In the phase locking and ratcheting states, the skyrmions undergo intricate 2D orbits induced by the Magnus term.

Effects of the substrate temperature on the properties of CuIn5S8 thin films

International Nuclear Information System (INIS)

Gannouni, M.; Kanzari, M.

2011-01-01

Structural, optical and electrical properties of CuIn 5 S 8 thin films grown by thermal evaporation have been studied relating the effects of substrate heating conditions of these properties. The CuIn 5 S 8 thin films were carried out at substrate temperatures in the temperature range 100-300 deg. C. The effects of heated substrate on their physico-chemical properties were investigated using X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), optical transmission and hot probe method. X-ray diffraction revealed that the films are strong preferred orientation along the (3 1 1) plane upon substrate temperature 200 deg. C and amorphous for the substrate temperatures below 200 deg. C. No secondary phases are observed for all the films. The composition is greatly affected by heated substrate. From the optical transmission and reflection, an important absorption coefficient exceeds 10 5 cm -1 at 800 nm was found. As increasing the substrate temperature, the optical energy band gap decreases from 1.70 eV for the unheated films to 1.25 eV for the deposited films at 300 deg. C. It was found that CuIn 5 S 8 thin film is an n-type semiconductor at 250 deg. C.

Gene expression profiling following maternal deprivation: Involvement of the brain renin-angiotensin system

Directory of Open Access Journals (Sweden)

Claudia Liebl

2009-05-01

Full Text Available The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP, where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differentially regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently up-regulated genes, angiotensinogen, was validated using in-situ hybridization. Angiotensinogen is the precursor of angiotensin II, the main effector of the brain renin-angiotensin system (RAS, which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1 antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain a nd ACTH release following maternal separation. AT(1 receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and contribute to identifying signaling cascades that control stress system activity in the neonate.

EFFECT OF PLANT EXTRACTS AND GROWTH SUBSTRATES ON CONTROLLING DAMPING-OFF IN PINUS TECUNUMANII SEEDLINGS

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Maria Alejandra Fajardo-Mejía

2016-09-01

Full Text Available Damping-off is considered one of the most limiting phytosanitary problems in conifer seedling production because it may cause massive damage or total plant death in short time periods. This pathology is caused by a complex of microorganisms, the most common of which are Fusarium spp. and Rhizoctonia spp. This study evaluated the effect of growth substrates and plant extracts at different concentrations on germination and incidence of disease in Pinus tecunumanii plants. The plants were inoculated with the damping-off pathogen Fusarium oxysporum and treatments were applied in a completely randomized design with a factorial arrangement of 4x2x3. This corresponded to four substrates (pine bark, rice hull, coconut husk and sandy soil (4:1; two plant extracts (Matricaria chamomilla and Datura stramonium, andthree concentrations of each extract (Control concentration: 0%, Concentration 1: 50 % and Concentration 2: Undiluted. Each treatment had three repetitions, with 25 plants per repetition. The growth substrates affected germination; the most effective of these were sandy soil (4:1 and pine bark, with 90% and 92% germination at day 20, respectively. No significant difference was observed between the germination obtained with these substrates and that obtained with coconut husk after day 19. Meanwhile, all of the extracts had a significant effect on controlling the disease when they were combined with the substrates, with the exception of coconut husk. With this last substrate the incidence of disease was lower than 4% without the application of plant extracts; this indicates that coconut husk discourages the development of the disease on its own.

Oxidative Stress/Angiotensinogen/Renin-Angiotensin System Axis in Patients with Diabetic Nephropathy

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Masumi Kamiyama

2013-11-01

Full Text Available Although recent studies have proven that renin-angiotensin system (RAS blockades retard the progression of diabetic nephropathy, the detailed mechanisms of their reno-protective effects on the development of diabetic nephropathy remain uncertain. In rodent models, it has been reported that reactive oxygen species (ROS are important for intrarenal angiotensinogen (AGT augmentation in the progression of diabetic nephropathy. However, no direct evidence is available to demonstrate that AGT expression is enhanced in the kidneys of patients with diabetes. To examine whether the expression levels of ROS- and RAS-related factors in kidneys are increased with the progression of diabetic nephropathy, biopsied samples from 8 controls and 27 patients with type 2 diabetes were used. After the biopsy, these patients were diagnosed with minor glomerular abnormality or diabetes mellitus by clinical and pathological findings. The intensities of AGT, angiotensin II (Ang II, 4-hydroxy-2-nonenal (4-HNE, and heme oxygenase-1 (HO-1 were examined by fluorescence in situ hybridization and/or immunohistochemistry. Expression levels were greater in patients with diabetes than in control subjects. Moreover, the augmented intrarenal AGT mRNA expression paralleled renal dysfunction in patients with diabetes. These data suggest the importance of the activated oxidative stress/AGT/RAS axis in the pathogenesis of diabetic nephropathy.

The effect of microstructure at interface between coating and substrate on damping capacity of coating systems

International Nuclear Information System (INIS)

Wang, Xueqin; Pei, Yanling; Ma, Yue

2013-01-01

Samples with various interface microstructures between the coating and the substrate were designed and fabricated in this paper. Dynamic mechanical thermal analyzer (DMTA) was utilized to investigate the dynamic mechanical properties of the samples and scanning electron microscopy (SEM) was used to observe the interface microstructure between the substrate and coating. The effect of the interface microstructure on damping was studied, and results indicated that the larger the coating/substrate interface thickness was and the more interface defects were, the higher interface system damping was. When the micro-hardness ratio of substrate to coating was increased, the damping of coating system was enhanced. The effect of the APS and EB-PVD coating on damping capacity was investigated. There was a dramatic increase in the damping value of the APS coating when the strain was higher than 20 ppm, while the damping amplitude effect of the EB-PVD coating was not so obvious, which could mainly be caused by the different energy dissipation mechanisms of the two coatings.

Improving surface-enhanced Raman scattering effect using gold-coated hierarchical polystyrene bead substrates modified with postgrowth microwave treatment.

Science.gov (United States)

Yuen, Clement; Zheng, Wei; Huang, Zhiwei

2008-01-01

We report a novel postgrowth microwave heating implementation by selectively modifying hierarchical polystyrene (PS) bead substrates coated with gold (Au) films to effectively improve the surface-enhanced Raman scattering (SERS) effect on the analytes. The SERS signal of probe molecule rhodamine 6G (Rh 6G) on the microwave-treated Au-PS substrates can be improved by 10-fold, while the detection limit of Rh 6G in concentration can be enhanced by two orders of magnitude compared to the as-growth substrates. The high-quality SERS spectrum of saliva can also be acquired using the modified substrates, demonstrating the potential for the realization of the high-performance SERS substrates for biomedical applications.

Potential impact of renin-angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients

International Nuclear Information System (INIS)

Nakagawa, Naoki; Yao, Naoyuki; Hirayama, Tomoya

2011-01-01

Although metabolic syndrome confers an increased risk of cardiovascular disease in the general population, little is known about the alteration of abdominal adiposity and its association with adipocytokines in hemodialysis patients. We investigated the plasma high-molecular-weight (HMW) adiponectin level and its relationship to visceral fat area (VFA) and various markers of atherosclerosis in hemodialysis patients. In a cross-sectional study, conventional cardiovascular risk factors, plasma total and HMW adiponectin, the number of components of the metabolic syndrome and, using computed tomography, the distribution of abdominal adiposity were assessed in 144 hemodialysis patients (90 men and 54 women; mean age, 60.7 years) and 30 age- and sex-matched patients with chronic kidney disease (CKD). Plasma HMW adiponectin levels in hemodialysis patients were significantly higher than those in patients with CKD, negatively associated with VFA and serum triglycerides and positively associated with plasma total adiponectin, as well as the HMW-to-total adiponectin ratio in men and women (all P<0.05) in a simple regression analysis. In a multiple regression analysis, VFA was a significant determinant of HMW adiponectin in hemodialysis patients. Furthermore, after adjustment for classical risk factors, HMW adiponectin levels were significantly higher in patients undergoing treatment with renin-angiotensin system inhibitors or calcium channel blockers compared with patients not undergoing such treatment. This study shows that plasma HMW adiponectin levels were negatively associated with VFA and positively associated with treatment with blockade of the renin-angiotensin system and of the calcium channel. Therefore, these drugs might be effective for improving adipocytokine-related metabolic abnormalities in hemodialysis patients. (author)

Analysis of effect of nanoporous alumina substrate coated with polypyrrole nanowire on cell morphology based on AFM topography.

Science.gov (United States)

El-Said, Waleed Ahmed; Yea, Cheol-Heon; Jung, Mi; Kim, Hyuncheol; Choi, Jeong-Woo

2010-05-01

In this study, in situ electrochemical synthesis of polypyrrole nanowires with nanoporous alumina template was described. The formation of highly ordered porous alumina substrate was demonstrated with Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). In addition, Fourier transform infrared analysis confirmed that polypyrrole (PP) nanowires were synthesized by direct electrochemical oxidation of pyrrole. HeLa cancer cells and HMCF normal cells were immobilized on the polypyrrole nanowires/nanoporous alumina substrates to determine the effects of the substrate on the cell morphology, adhesion and proliferation as well as the biocompatibility of the substrate. Cell adhesion and proliferation were characterized using a standard MTT assay. The effects of the polypyrrole nanowires/nanoporous alumina substrate on the cell morphology were studied by AFM. The nanoporous alumina coated with polypyrrole nanowires was found to exhibit better cell adhesion and proliferation than polystyrene petridish, aluminum foil, 1st anodized and uncoated 2nd anodized alumina substrate. This study showed the potential of the polypyrrole nanowires/nanoporous alumina substrate as biocompatibility electroactive polymer substrate for both healthy and cancer cell cultures applications.

Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

Science.gov (United States)

Qian, Xiaobing; Lin, Leilei; Zong, Yao; Yuan, Yongguang; Dong, Yanmin; Fu, Yue; Shao, Wanwen; Li, Yujie; Gao, Qianying

2018-03-01

This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2 + pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

Effect of radiation-induced substrate defects on microstrip gas chamber gain behaviour

International Nuclear Information System (INIS)

Pallares, A.; Brom, J.M.; Bergdolt, A.M.; Coffin, J.; Eberle, H.; Sigward, M.H.; Fontaine, J.C.; Barthe, S.; Schunck, J.P.

1998-01-01

The aim of this work was to quantify the influence of radiation-induced substrate defects on microstrip gas chamber (MSGC) gain behaviour. The first part of this paper focuses on radiation effects on a typical MSGC substrate: Desag D263 glass. Defect generation was studied for Desag D263 with pure silica (Suprasil 1) as a reference. We studied the evolution of defect concentration with respect to accumulated doses up to 480 kGy. Annealing studies of defects in Desag D263 were also performed. In the second part, the radiation sensitivity of Desag D263 glass has been linked to the behaviour of the detector under irradiation. Comparative gain measurements were taken before and after substrate irradiation at 10 and 80 kGy the minimal dose received during LHC operation and the dose for which defect density is maximum (respectively). (orig.)

Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

Science.gov (United States)

Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

2016-04-01

Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Substrate and p-layer effects on polymorphous silicon solar cells

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Abolmasov S.N.

2014-07-01

Full Text Available The influence of textured transparent conducting oxide (TCO substrate and p-layer on the performance of single-junction hydrogenated polymorphous silicon (pm-Si:H solar cells has been addressed. Comparative studies were performed using p-i-n devices with identical i/n-layers and back reflectors fabricated on textured Asahi U-type fluorine-doped SnO2, low-pressure chemical vapor deposited (LPCVD boron-doped ZnO and sputtered/etched aluminum-doped ZnO substrates. The p-layers were hydrogenated amorphous silicon carbon and microcrystalline silicon oxide. As expected, the type of TCO and p-layer both have a great influence on the initial conversion efficiency of the solar cells. However they have no effect on the defect density of the pm-Si:H absorber layer.

Effect of substrate temperature on the morphological, structural, and optical properties of RF sputtered Ge1−x Snx films on Si substrate

International Nuclear Information System (INIS)

Mahmodi, H; Hashim, M R

2017-01-01

In this study, Ge 1−x Sn x alloy films are co-sputtered on Si(100) substrates using RF magnetron sputtering at different substrate temperatures. Scanning electron micrographs, atomic force microscopy (AFM), Raman spectroscopy, and x-ray photoemission spectroscopy (XPS) are conducted to investigate the effect of substrate temperature on the structural and optical properties of grown GeSn alloy films. AFM results show that RMS surface roughness of the films increases from 1.02 to 2.30 nm when raising the substrate temperature. This increase could be due to Sn surface segregation that occurs when raising the substrate temperature. Raman spectra exhibits the lowest FWHM value and highest phonon intensity for a film sputtered at 140 °C. The spectra show that decreasing the deposition temperature to 140 °C improves the crystalline quality of the alloy films and increases nanocrystalline phase formation. The results of Raman spectra and XPS confirm Ge–Sn bond formation. The optoelectronic characteristics of fabricated metal-semiconductor-metal photodetectors on sputtered samples at room temperature (RT) and 140 °C are studied in the dark and under illumination. The sample sputtered at 140 °C performs better than the RT sputtered sample. (paper)

Sonochemically synthesized Ag nanoparticles as a SERS active substrate and effect of surfactant

Energy Technology Data Exchange (ETDEWEB)

Dar, Nitzan, E-mail: n58987012@mail.ncku.edu.tw [Department of Material Science and Engineering, National Cheng Kung University, Tainan 70101 Taiwan (China); Chen, Kuang-Yu [Department of Material Science and Engineering, National Cheng Kung University, Tainan 70101 Taiwan (China); Nien, Yung-Tang, E-mail: ytnien@nfu.edu.tw [Department of Materials Science and Engineering, National Formosa University, Huwei, Yunlin 63201, Taiwan (China); Perkas, Nina [Institute of nanotechnology and advanced materials, Department of Chemistry, Bar-Ilan University, Ramat-Gan 5290002 (Israel); Gedanken, Aharon, E-mail: Aharon.Gedanken@biu.ac.il [Institute of nanotechnology and advanced materials, Department of Chemistry, Bar-Ilan University, Ramat-Gan 5290002 (Israel); Chen, In-Gann, E-mail: ingann@mail.ncku.edu.tw [Department of Material Science and Engineering, National Cheng Kung University, Tainan 70101 Taiwan (China)

2015-03-15

Highlights: • Solid state Ag SERS active substrates were sonochemically synthesized. • High intensity SERS spectra of both crystal violet and rhodamine 6G were observed. • We discovered that PVP aided synthesized substrates showed higher SERS intensity. - Abstract: Surface enhanced Raman scattering (SERS) enables the detection of substances at low concentrations using silver or gold nanostructure. The SERS technique has many applications, such as environmental detection and biosensing. Sonochemistry is an excellent and cheap deposition technique for coating substrates in a form of nanostructure at ambient temperature. It can also be utilized to prepare large SERS substrates. Here, we used the advantages of sonochemistry to deposit solid SERS substrates immobilized on GaN nanostructure. Morphology was studied by scanning electron microscopy. The elemental composition and the spatial distribution were examined by energy dispersive X-ray spectroscopy. The crystal structure and atomic presence was confirmed by X-ray diffraction. SERS substrates were examined with the analytes crystal violet (10{sup −5} M) and rhodamine 6G (10{sup −6} M), they showed prominent characteristic peaks. We discovered that the SERS intensity of poly-vinyl-pyrrolidinone aided sonochemical deposition of Ag nanoparticles was increased. The reason for the effect is morphological changes of the Ag nanoparticles. Smaller nanoparticles were fabricated, which increase their SERS intensity.

Considerations in the selection of model substrates for microbiological effects research

International Nuclear Information System (INIS)

Francis, A.J.; Rose, A.W.

1984-01-01

The physical and chemical characteristics of several energy residues have been briefly reviewed in order to select a model or representative substrate of basic research to determine the significance of anaerobic microbial dissolution and mobilization or immobilization of toxic trace elements under subsurface environmental conditions. The major factors which influence the dissolution and mobilization of trace metals have been critically examined, e.g., (i) effects on pH of leachates (pyrite oxidation), soluble acid, and basic compounds; (ii) effects on oxidation state of leachates (oxidation state of Fe, presence of organics); (iii) concentration of toxic inorganic species, and chemical form; (iv) surface area of waste particles; and (v) physical strength and particle size, with resulting effects on permeability of the substrate. Several major physical and chemical characteristics are common to energy-related residues yet each of these materials has a unique set of physical and chemical properties. The pros and cons of selecting a single model substrate for microbiological research were discussed at the Geochemical and Biochemical Working Group Meeting and use of the end-member concept was suggested. From the abundance, distribution, forms of trace metals present, and volume of these metal-containing residues disposed of in the subsurface environments, microbiological studies can be performed with coal beneficiation and coal gasification residues under a variety of subsurface environmental conditions, and results can be validated in the field. The basic scientific information obtained from this research can be applied to other materials of similar composition. 18 references, 3 figures, 7 tables

Relative Atrial Natriuretic Peptide Deficiency and Inadequate Renin and Angiotensin II Suppression in Obese Hypertensive Men

DEFF Research Database (Denmark)

Asferg, Camilla L; Nielsen, Søren J; Andersen, Ulrik B

2013-01-01

Obesity is a strong risk factor for hypertension, but the mechanisms by which obesity leads to hypertension are incompletely understood. On this background, we assessed dietary sodium intake, serum levels of natriuretic peptides (NPs), and the activity of the renin-angiotensin system in 63 obese...... hypertensive men (obeseHT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure, ≥130/80 mm Hg), in 40 obese normotensive men (obeseNT: body mass index, ≥30.0 kg/m(2); 24-hour ambulatory blood pressure,...

Effects of drilling muds on behavior of the American lobster, Homarus americanus, in water column and substrate exposures

Energy Technology Data Exchange (ETDEWEB)

Atema, J; Leavitt, D F; Barshaw, D E; Cuomo, M C

1982-01-01

Studies were conducted to explore the effects of drilling muds on various aspects of lobster behavior directly related to survival in the field. Toxicity of different drilling muds varied from immediately lethal to adult lobsters to apparently harmless to postlarval stages, with a variety of intermediate effects. Both the chemical toxicity in the water column and the physical effects of covering the substrate with drilling mud were studied, and both interfered with normal lobster behavior. The studies are mainly concerned with postlarval lobsters (stages IV and V), just after settling on the bottom. They were tested in 36-d chronic exposures (7 mg/L) and in seminatural aquaria with 1-mm layers of drilling mud covering the substrate. Toxicity in the water column manifested itself in feeding and molting delays, severe delays in shelter construction, increased walking and swimming, unprovoked tail flipping, and lethargy. A natural bay mud used as a control caused no such effects. Physical effects of substrate cover were apparent in experiments with 1-, 2-, and 4-mm layers of drilling mud and similar layers of a mixture of bentonite and barite covering a natural mud substrate. In depths of 4mm both kinds of substrate cover caused severe delays in shelter construction and in quality of burrows constructed. Thus, substrates with 4-mm to perhaps as little as 1-mm covering of drilling mud may cause increased exposure of lobsters to predators and currents, resulting in the substrate becoming unsuitable for lobster settling and survival.

Simultaneous evaluation of effective diffusion coefficients of the substrates in a biofilm with a novel experimental method

Energy Technology Data Exchange (ETDEWEB)

Beyenal, H.; Tanyolac, A. [Hacettepe Univ., Ankara (Turkey)

1996-08-01

A pure culture of Zoogloea ramigera was grown as a film on active carbon particles in a differential fluidized bed biofilm reactor. Pseudo-steady state conditions were established within this reactor and thus, the stable substrate concentrations and flux values were obtained within definite time intervals, along with homogeneous biofilm thickness and density. The free-growth kinetics of the culture were studied in a continuous fermenter and a multi-substrate growth model was used to describe the utilization of limiting substrate in the biofilm. The limiting substrates for the culture were determined to be glucose, ammonium and oxygen. The effective diffusion coefficients of these substrates were calculated simultaneously with a diffusion-reaction model. Results of the model solution revealed that the effective diffusion coefficient for all three substrates through the biofilm decreased with increased biofilm density and observed biofilm thickness up to a critical value of about 90 x 10{sup -6} m. After this critical point, all diffusion coefficients started to increase slowly due to diminished biofilm density. 31 refs., 4 figs., 4 tabs.

A comparative study of graphene and graphite-based field effect transistor on flexible substrate

Science.gov (United States)

Bhatt, Kapil; Rani, Cheenu; Vaid, Monika; Kapoor, Ankit; Kumar, Pramod; Kumar, Sandeep; Shriwastawa, Shilpi; Sharma, Sandeep; Singh, Randhir; Tripathi, C. C.

2018-06-01

In the present era, there has been a great demand of cost-effective, biodegradable, flexible and wearable electronics which may open the gate to many applications like flexible displays, RFID tags, health monitoring devices, etc. Due to the versatile nature of plastic substrates, they have been extensively used in packaging, printing, etc. However, the fabrication of electronic devices requires specially prepared substrates with high quality surfaces, chemical compositions and solutions to the related fabrication issues along with its non-biodegradable nature. Therefore, in this report, a cost-effective, biodegradable cellulose paper as an alternative dielectric substrate material for the fabrication of flexible field effect transistor (FET) is presented. The graphite and liquid phase exfoliated graphene have been used as the material for the realisation of source, drain and channel on cellulose paper substrate for its comparative analysis. The mobility of fabricated FETs was calculated to be 83 cm2/V s (holes) and 33 cm2/V s (electrons) for graphite FET and 100 cm2/V s (holes) and 52 cm2/V s (electrons) for graphene FET, respectively. The output characteristic of the device demonstrates the linear behaviour and a comprehensive increase in conductance as a function of gate voltages. The fabricated FETs may be used for strain sensing, health care monitoring devices, human motion detection, etc.

Effect of Substrate Roughness on Adhesion and Structural Properties of Ti-Ni Shape Memory Alloy Thin Film.

Science.gov (United States)

Kim, Donghwan; Lee, Hyunsuk; Bae, Joohyeon; Jeong, Hyomin; Choi, Byeongkeun; Nam, Taehyun; Noh, Jungpil

2018-09-01

Ti-Ni shape memory alloy (SMA) thin films are very attractive material for industrial and medical applications such as micro-actuator, micro-sensors, and stents for blood vessels. An important property besides shape memory effect in the application of SMA thin films is the adhesion between the film and the substrate. When using thin films as micro-actuators or micro-sensors in MEMS, the film must be strongly adhered to the substrate. On the other hand, when using SMA thin films in medical devices such as stents, the deposited alloy thin film must be easily separable from the substrate for efficient processing. In this study, we investigated the effect of substrate roughness on the adhesion of Ti-Ni SMA thin films, as well as the structural properties and phase-transformation behavior of the fabricated films. Ti-Ni SMA thin films were deposited onto etched glass substrates with magnetron sputtering. Radio frequency plasma was used for etching the substrate. The adhesion properties were investigated through progressive scratch test. Structural properties of the films were determined via Feld emission scanning electron microscopy, X-ray diffraction measurements (XRD) and Energy-dispersive X-ray spectroscopy analysis. Phase transformation behaviors were observed with differential scanning calorimetry and low temperature-XRD. Ti-Ni SMA thin film deposited onto rough substrate provides higher adhesive strength than smooth substrate. However the roughness of the substrate has no influence on the growth and crystallization of the Ti-Ni SMA thin films.

Effect of modified ITO substrate on electrochromic properties of polyaniline films

Energy Technology Data Exchange (ETDEWEB)

Leon-Silva, U.; Nicho, M.E.; Cruz-Silva, Rodolfo [Centro de Investigacion en Ingenieria y Ciencias Aplicadas, UAEMor, Av. Universidad 1001, Col. Chamilpa, 62209, Cuernavaca, Morelos (Mexico); Hu, Hailin [Departamento de Materiales Solares, Centro de Investigacion en Energia, UNAM, Av. Xochicalco S/N, Temixco, 62580, Morelos (Mexico)

2007-09-22

In this work, we report the morphological and electrochromic properties of electrochemically synthesized polyaniline (PANI) thin films on bare and modified indium-tin oxide (ITO) glass substrates. In the last case, the surface of ITO glass was covered by a self-assembled monolayer of N-phenyl-{gamma}-aminopropyl-trimethoxysilane (PAPTS). Atomic force microscopy images and perfilometry show that smoother and thinner PANI films were grown on PAPTS-modified ITO substrates. PANI-based electrochromic devices (ECDs) were assembled by using a viscous polymeric electrolyte (PE) of LiClO{sub 4} and polymethyl methacrylate (PMMA) co-dissolved in a mixture of propylene and ethylene carbonate. The architectural design of the devices was glass/ITO/PANI/PE/ITO/glass. A dual ECD was also prepared by collocating a poly(3-methylthiophene) (P3MT) thin film as a complementary electrochromic element. The effect of the PAPTS-modified ITO substrate is reflected in a higher optical transmittance at bleach state and a little less color change at 550 nm of PANI-based ECDs. (author)

Effect of radiation-induced substrate defects on microstrip gas chamber gain behaviour

Energy Technology Data Exchange (ETDEWEB)

Pallares, A.; Brom, J.M.; Bergdolt, A.M.; Coffin, J.; Eberle, H.; Sigward, M.H. [Institute de Recherches Subatomiques, 67 - Strasbourg (France); Fontaine, J.C. [Universite de Haute Alsace, GRPHE, 61 rue Albert Camus, 68093 Mulhouse Cedex (France); Barthe, S.; Schunck, J.P. [Laboratoire PHASE (UPR 292 du CNRS), 23 rue du Loess, BP 28, 67037 Strasbourg Cedex 2 (France)

1998-08-01

The aim of this work was to quantify the influence of radiation-induced substrate defects on microstrip gas chamber (MSGC) gain behaviour. The first part of this paper focuses on radiation effects on a typical MSGC substrate: Desag D263 glass. Defect generation was studied for Desag D263 with pure silica (Suprasil 1) as a reference. We studied the evolution of defect concentration with respect to accumulated doses up to 480 kGy. Annealing studies of defects in Desag D263 were also performed. In the second part, the radiation sensitivity of Desag D263 glass has been linked to the behaviour of the detector under irradiation. Comparative gain measurements were taken before and after substrate irradiation at 10 and 80 kGy the minimal dose received during LHC operation and the dose for which defect density is maximum (respectively). (orig.) 26 refs.

Effects of different substrates on the yield and protein content of ...

African Journals Online (AJOL)

The effects of seven substrates for the cultivation, yield and protein content of the mushroom, Pleurotus tuberregium (Fries) Singer were investigated. The experimental design used was completely randomized design (CRD) of 7 treatments and 10 replicates. The highest fresh weight yield was obtained from mushrooms ...

Effect of sputtering parameters on optical and electrical properties of ITO films on PET substrates

International Nuclear Information System (INIS)

Tseng, Kun-San; Lo, Yu-Lung

2013-01-01

The optical and electrical properties of indium tin oxide (ITO) thin films deposited on flexible polyethylene terephthalate (PET) substrates using a DC magnetron sputtering technique are investigated as a function of the deposition time, the argon flow rate and the target–substrate distance. It is found that all of the ITO films contain a high fraction of amorphous phase. The volume fraction of crystallite precipitates in the amorphous host increases with an increasing deposition time or a reducing argon flow rate. The deposition time and argon flow rate have higher effects on the optical transparency of the ITO films than the target–substrate distance has. Increasing film thickness is not the only reason for the transmittance reduced. It is found that an increase of the extinction coefficient by increasing deposition time or an increase of the refractive index by decreasing argon flow rate also reduces the transmittance of thin film. For a constant deposition time, the resistivity of the ITO films reduces with a reducing argon flow rate or a reducing target–substrate distance. For a constant argon flow rate, a critical value of the deposition time exists at which both the resistivity and the effect of the target–substrate distance are minimized. Finally, it is concluded that the film resistivity has low sensitivity to the target–substrate distance if the best deposition conditions which mostly attain the lowest resistivity are matched.

Effect of sputtering parameters on optical and electrical properties of ITO films on PET substrates

Science.gov (United States)

Tseng, Kun-San; Lo, Yu-Lung

2013-11-01

The optical and electrical properties of indium tin oxide (ITO) thin films deposited on flexible polyethylene terephthalate (PET) substrates using a DC magnetron sputtering technique are investigated as a function of the deposition time, the argon flow rate and the target-substrate distance. It is found that all of the ITO films contain a high fraction of amorphous phase. The volume fraction of crystallite precipitates in the amorphous host increases with an increasing deposition time or a reducing argon flow rate. The deposition time and argon flow rate have higher effects on the optical transparency of the ITO films than the target-substrate distance has. Increasing film thickness is not the only reason for the transmittance reduced. It is found that an increase of the extinction coefficient by increasing deposition time or an increase of the refractive index by decreasing argon flow rate also reduces the transmittance of thin film. For a constant deposition time, the resistivity of the ITO films reduces with a reducing argon flow rate or a reducing target-substrate distance. For a constant argon flow rate, a critical value of the deposition time exists at which both the resistivity and the effect of the target-substrate distance are minimized. Finally, it is concluded that the film resistivity has low sensitivity to the target-substrate distance if the best deposition conditions which mostly attain the lowest resistivity are matched.

Effect of sputtering parameters on optical and electrical properties of ITO films on PET substrates

Energy Technology Data Exchange (ETDEWEB)

Tseng, Kun-San [Department of Mechanical Engineering, National Cheng Kung University, Tainan, Taiwan (China); Lo, Yu-Lung, E-mail: loyl@mail.ncku.edu.tw [Department of Mechanical Engineering, National Cheng Kung University, Tainan, Taiwan (China); Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan (China)

2013-11-15

The optical and electrical properties of indium tin oxide (ITO) thin films deposited on flexible polyethylene terephthalate (PET) substrates using a DC magnetron sputtering technique are investigated as a function of the deposition time, the argon flow rate and the target–substrate distance. It is found that all of the ITO films contain a high fraction of amorphous phase. The volume fraction of crystallite precipitates in the amorphous host increases with an increasing deposition time or a reducing argon flow rate. The deposition time and argon flow rate have higher effects on the optical transparency of the ITO films than the target–substrate distance has. Increasing film thickness is not the only reason for the transmittance reduced. It is found that an increase of the extinction coefficient by increasing deposition time or an increase of the refractive index by decreasing argon flow rate also reduces the transmittance of thin film. For a constant deposition time, the resistivity of the ITO films reduces with a reducing argon flow rate or a reducing target–substrate distance. For a constant argon flow rate, a critical value of the deposition time exists at which both the resistivity and the effect of the target–substrate distance are minimized. Finally, it is concluded that the film resistivity has low sensitivity to the target–substrate distance if the best deposition conditions which mostly attain the lowest resistivity are matched.

Substrate effect on oxygen reduction electrocatalysis

International Nuclear Information System (INIS)

Timperman, L.; Feng, Y.J.; Vogel, W.; Alonso-Vante, N.

2010-01-01

The oxygen reduction reaction (ORR) was investigated on carbon (XC-72) supported platinum nanoparticles, generated via the carbonyl chemical route and on oxide composites supported platinum generated via the UV-photo-deposition technique in sulfuric acid medium. The behavior of Pt/C was examined using a careful dosing of the catalyst loading spanning the range from 4.3 to 131 μg cm -2 . The ORR electrochemical response of Pt/C (in line with recent literature data) is put into contrast with the Pt/oxide-composite systems. Our results point out that it is possible to use smaller amounts of catalyst for the ORR when platinum atoms interact with the oxide (anatase) surface of the substrate composite. Evidence of the incipient metal-substrate interaction is discussed in the light of the results of XRD experiments.

Effect of substrate rotation on domain structure and magnetic relaxation in magnetic antidot lattice arrays

International Nuclear Information System (INIS)

Mallick, Sougata; Mallik, Srijani; Bedanta, Subhankar

2015-01-01

Microdimensional triangular magnetic antidot lattice arrays were prepared by varying the speed of substrate rotation. The pre-deposition patterning has been performed using photolithography technique followed by a post-deposition lift-off. Surface morphology taken by atomic force microscopy depicted that the growth mechanism of the grains changes from chain like formation to island structures due to the substrate rotation. Study of magnetization reversal via magneto optic Kerr effect based microscopy revealed reduction of uniaxial anisotropy and increase in domain size with substrate rotation. The relaxation measured under constant magnetic field becomes faster with rotation of the substrate during deposition. The nature of relaxation for the non-rotating sample can be described by a double exponential decay. However, the relaxation for the sample with substrate rotation is well described either by a double exponential or a Fatuzzo-Labrune like single exponential decay, which increases in applied field

Substrate Effect on Plasma Clean Efficiency in Plasma Enhanced Chemical Vapor Deposition System

Directory of Open Access Journals (Sweden)

Shiu-Ko JangJian

2007-01-01

Full Text Available The plasma clean in a plasma-enhanced chemical vapor deposition (PECVD system plays an important role to ensure the same chamber condition after numerous film depositions. The periodic and applicable plasma clean in deposition chamber also increases wafer yield due to less defect produced during the deposition process. In this study, the plasma clean rate (PCR of silicon oxide is investigated after the silicon nitride deposited on Cu and silicon oxide substrates by remote plasma system (RPS, respectively. The experimental results show that the PCR drastically decreases with Cu substrate compared to that with silicon oxide substrate after numerous silicon nitride depositions. To understand the substrate effect on PCR, the surface element analysis and bonding configuration are executed by X-ray photoelectron spectroscopy (XPS. The high resolution inductively coupled plasma mass spectrometer (HR-ICP-MS is used to analyze microelement of metal ions on the surface of shower head in the PECVD chamber. According to Cu substrate, the results show that micro Cu ion and the CuOx bonding can be detected on the surface of shower head. The Cu ion contamination might grab the fluorine radicals produced by NF3 ddissociation in the RPS and that induces the drastic decrease on PCR.

Modeling the Substrate Skin Effects in Mutual RL Characteristics.,

Directory of Open Access Journals (Sweden)

D. de Roest

2003-12-01

Full Text Available The goal of this work was to model the influence of the substrateskin effects on the distributed mutual impedance per unit lengthparameters of multiple coupled on-chip interconnects. The proposedanalytic model is based on the frequency-dependent distribution of thecurrent in the silicon substrate and the closed form integrationapproach. It is shown that the calculated frequency-dependentdistributed mutual inductance and the associated mutual resistance arein good agreement with the results obtained from CAD-oriented circuitmodeling technique.

Phonon scattering in graphene over substrate steps

DEFF Research Database (Denmark)

Sevincli, Haldun; Brandbyge, Mads

2014-01-01

We calculate the effect on phonon transport of substrate-induced bends in graphene. We consider bending induced by an abrupt kink in the substrate, and provide results for different step-heights and substrate interaction strengths. We find that individual substrate steps reduce thermal conductance...

The role of local renin-angiotensin system in arterial chemoreceptors in sleep-breathing disorders

Directory of Open Access Journals (Sweden)

Man Lung eFung

2014-09-01

Full Text Available The renin-angiotensin system (RAS plays pivotal roles in the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Experimental studies have demonstrated a locally expressed RAS in the carotid body, which is functional significant in the effect of angiotensin peptides on the regulation of the activity of peripheral chemoreceptors and the chemoreflex. The physiological and pathophysiological implications of the RAS in the carotid body have been proposed upon recent studies showing a significant upregulation of the RAS expression under hypoxic conditions relevant to altitude acclimation and sleep apnea and also in animal model of heart failure. Specifically, the increased expression of angiotensinogen, angiotensin-converting enzyme and angiotensin AT1 receptors plays significant roles in the augmented carotid chemoreceptor activity and inflammation of the carotid body. This review aims to summarize these results with highlights on the pathophysiological function of the RAS under hypoxic conditions. It is concluded that the maladaptive changes of the RAS in the carotid body plays a pathogenic role in sleep apnea and heart failure, which could potentially be a therapeutic target for the treatment of the pathophysiological consequence of sleep apnea.

Role of MicroRNAs in Renin-Angiotensin-Aldosterone System-Mediated Cardiovascular Inflammation and Remodeling

Directory of Open Access Journals (Sweden)

Maricica Pacurari

2015-01-01

Full Text Available MicroRNAs are endogenous regulators of gene expression either by inhibiting translation or protein degradation. Recent studies indicate that microRNAs play a role in cardiovascular disease and renin-angiotensin-aldosterone system- (RAAS- mediated cardiovascular inflammation, either as mediators or being targeted by RAAS pharmacological inhibitors. The exact role(s of microRNAs in RAAS-mediated cardiovascular inflammation and remodeling is/are still in early stage of investigation. However, few microRNAs have been shown to play a role in RAAS signaling, particularly miR-155, miR-146a/b, miR-132/122, and miR-483-3p. Identification of specific microRNAs and their targets and elucidating microRNA-regulated mechanisms associated RAS-mediated cardiovascular inflammation and remodeling might lead to the development of novel pharmacological strategies to target RAAS-mediated vascular pathologies. This paper reviews microRNAs role in inflammatory factors mediating cardiovascular inflammation and RAAS genes and the effect of RAAS pharmacological inhibition on microRNAs and the resolution of RAAS-mediated cardiovascular inflammation and remodeling. Also, this paper discusses the advances on microRNAs-based therapeutic approaches that may be important in targeting RAAS signaling.

Substrate Screening Effects in ab initio Many-body Green's Function Calculations of Doped Graphene on SiC

Science.gov (United States)

Vigil-Fowler, Derek; Lischner, Johannes; Louie, Steven

2013-03-01

Understanding many-electron interaction effects and the influence of the substrate in graphene-on-substrate systems is of great theoretical and practical interest. Thus far, both model Hamiltonian and ab initio GW calculations for the quasiparticle properties of such systems have employed crude models for the effect of the substrate, often approximating the complicated substrate dielectric matrix by a single constant. We develop a method in which the spatially-dependent dielectric matrix of the substrate (e.g., SiC) is incorporated into that of doped graphene to obtain an accurate total dielectric matrix. We present ab initio GW + cumulant expansion calculations, showing that both the cumulant expansion (to include higher-order electron correlations) and a proper account of the substrate screening are needed to achieve agreement with features seen in ARPES. We discuss how this methodology could be used in other systems. This work was supported by NSF Grant No. DMR10-1006184 and U.S. DOE Contract No. DE-AC02-05CH11231. Computational resources have been provided by the NERSC and NICS. D.V-F. acknowledges funding from the DOD's NDSEG fellowship.

Effect of Substrate Friction in a Two-Dimensional Granular Couette Shearing Cell

Science.gov (United States)

Templeman, Chris; Garg, Shila

2001-03-01

An investigation of the effect of substrate friction on the kinematics of rigid granular material in a two-dimensional granular Couette shearing cell was conducted. Cylindrical disks resting on a substrate were packed between a stationary outer ring and a rotating inner wheel. Previous work reports the velocity and particle rotation rates as a function of packing fraction and shearing rates [1]. The authors report the existence of a stick-slip condition of the disks in contact with the shearing wheel. The focus of our study is to investigate the impact of the substrate friction on the stick-slip condition as well as the kinematics of the system in general. [1] C.T. Veje, Daniel W. Howell, and R.P Behringer, Phys. Rev. E 59, 739 (1999). This research was partially supported by the Copeland Fund, administered by The College of Wooster. C.T. received support from NASA GRC LERCIP internship program.

Effect of substrate crystallographic orientation of garnet-ferrite film properties

International Nuclear Information System (INIS)

Burym, Yu.A.; Dubinko, S.V.; Mitsaj, Yu.N.; Borovitskaya, L.N.; Prokopov, A.P.

1992-01-01

Samples of garnet-ferrite films with a composition (YbGdPrBi) 3 (FeAlGa) 5 O 12 grown under identical conditions on variously oriented substrates, have been studied. The substrate orientation was changed in such a way that the vector of the substrate normal was in the [110] plane between the [111] and [112] directions. We have found that the substrate misorientation leads to an inclined position of the easy magnetization axis (EMA) and a reduction of the film growth rate. The change of the film physical properties (Faraday rotation, Curie temperature, magnetization) indicates the film composition variation with the substrate orientation change. The temperature dependence of the EMA slope angle in the studied samples is determined by the magnetoelastic contribution to the anisotropy constants. (author)

The effectiveness of various biofiltration substrates in removing bacteria, endotoxins, and dust from ventilation system exhaust from a chicken hatchery.

Science.gov (United States)

Tymczyna, L; Chmielowiec-Korzeniowska, A; Drabik, A

2007-10-01

The objective of this study was to evaluate the effectiveness of various organic and organic-mineral biofilter media in purifying ventilation exhaust from a chicken hatchery room. Three different substrates were tested. Efficiency levels for the removal of dust, gram-negative bacteria, and bacterial endotoxin were recorded. The microbiological properties of the substrates were also studied. All of the biofilter substrates were highly effective in removing gram-negative bacteria, moderately effective in reducing dust levels, and only slightly effective in removing endotoxin. The substrate that was most efficient in retaining bioaerosols was the organic-mineral medium containing 20% halloysite, 40% compost, and 40% peat, which generally had at least satisfactory efficiency values for removing all of the contaminants tested.

Differences in cortical and pituitary activity in response to hypoglycaemia and cognitive testing in healthy men with different basal activity of the renin-angiotensin system

DEFF Research Database (Denmark)

Bie-Olsen, Lise G; Pedersen-Bjergaard, Ulrik; Kjaer, Troels W

2010-01-01

INTRODUCTION: High renin-angiotensin system (RAS) activity has been associated with a high risk of severe hypoglycaemia in patients with type 1 diabetes and with cognitive deterioration during experimental hypoglycaemia in healthy subjects. The aim of this study was to describe possible differenc...

Root development during soil genesis: effects of root-root interactions, mycorrhizae, and substrate

Science.gov (United States)

Salinas, A.; Zaharescu, D. G.

2015-12-01

A major driver of soil formation is the colonization and transformation of rock by plants and associated microbiota. In turn, substrate chemical composition can also influence the capacity for plant colonization and development. In order to better define these relationships, a mesocosm study was set up to analyze the effect mycorrhizal fungi, plant density and rock have on root development, and to determine the effect of root morphology on weathering and soil formation. We hypothesized that plant-plant and plant-fungi interactions have a stronger influence on root architecture and rock weathering than the substrate composition alone. Buffalo grass (Bouteloua dactyloides) was grown in a controlled environment in columns filled with either granular granite, schist, rhyolite or basalt. Each substrate was given two different treatments, including grass-microbes and grass-microbes-mycorrhizae and incubated for 120, 240, and 480 days. Columns were then extracted and analyzed for root morphology, fine fraction, and pore water major element content. Preliminary results showed that plants produced more biomass in rhyolite, followed by schist, basalt, and granite, indicating that substrate composition is an important driver of root development. In support of our hypothesis, mycorrhizae was a strong driver of root development by stimulating length growth, biomass production, and branching. However, average root length and branching also appeared to decrease in response to high plant density, though this trend was only present among roots with mycorrhizal fungi. Interestingly, fine fraction production was negatively correlated with average root thickness and volume. There is also slight evidence indicating that fine fraction production is more related to substrate composition than root morphology, though this data needs to be further analyzed. Our hope is that the results of this study can one day be applied to agricultural research in order to promote the production of crops

Defect concentration in nitrogen-doped graphene grown on Cu substrate: A thickness effect

Energy Technology Data Exchange (ETDEWEB)

Sharma, Dhananjay K., E-mail: dhananjay@ua.pt [Department of Physics & CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro (Portugal); Department of Mechanical Engineering & Centre for Mechanical Technology & Automation, University of Aveiro, 3810-193 Aveiro (Portugal); Fateixa, Sara [Department of Chemistry & CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro (Portugal); Hortigüela, María J. [Department of Mechanical Engineering & Centre for Mechanical Technology & Automation, University of Aveiro, 3810-193 Aveiro (Portugal); Vidyasagar, Reddithota [Department of Physics & CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro (Portugal); Otero-Irurueta, Gonzalo [Department of Mechanical Engineering & Centre for Mechanical Technology & Automation, University of Aveiro, 3810-193 Aveiro (Portugal); Nogueira, Helena I.S. [Department of Chemistry & CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro (Portugal); Singh, Manoj Kumar [Department of Mechanical Engineering & Centre for Mechanical Technology & Automation, University of Aveiro, 3810-193 Aveiro (Portugal); Kholkin, Andrei, E-mail: kholkin@ua.pt [Department of Physics & CICECO – Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro (Portugal); School of Natural Sciences and Mathematics, Ural Federal University, 620000 Ekaterinburg (Russian Federation)

2017-05-15

Tuning the band-gap of graphene is a current need for real device applications. Copper (Cu) as a substrate plays a crucial role in graphene deposition. Here we report the fabrication of in-situ nitrogen (N) doped graphene via chemical vapor deposition (CVD) technique and the effect of Cu substrate thickness on the growth mechanism. The ratio of intensities of G and D peaks was used to evaluate the defect concentration based on local activation model associated with the distortion of the crystal lattice due to incorporation of nitrogen atoms into graphene lattice. The results suggest that Cu substrate of 20 µm in thickness exhibits higher defect density (1.86×10{sup 12} cm{sup −2}) as compared to both 10 and 25 µm thick substrates (1.23×10{sup 12} cm{sup −2} and 3.09×10{sup 11} cm{sup −2}, respectively). Furthermore, High Resolution -X-ray Photoelectron Spectroscopy (HR-XPS) precisely affirms ~0.4 at% of nitrogen intercalations in graphene. Our results show that the substitutional type of nitrogen doping dominates over the pyridinic configuration. In addition, X-ray diffraction (XRD) shows all the XRD peaks associated with carbon. However, the peak at ~24° is suppressed by the substrate peaks (Cu). These results suggest that nitrogen atoms can be efficiently incorporated into the graphene using thinner copper substrates, rather than the standard 25 µm ones. This is important for tailoring the properties by graphene required for microelectronic applications.

Effect of substrate temperature on orientation of subphthalocyanine molecule in organic photovoltaic cells

International Nuclear Information System (INIS)

Chou, Chi-Ta; Tang, Wei-Li; Tai, Yian; Lin, Chien-Hung; Liu, Chin-Hsin J.; Chen, Li-Chyong; Chen, Kuei-Hsien

2012-01-01

This study investigates the effect of substrate temperature (T s ) on the boron subphthalocyanine chloride (SubPc) thin film and its power conversion efficiency in SubPc/C 60 heterojunction photovoltaic cells. The orientations of SubPc molecules in thin films determined by X-ray diffraction is strongly correlated with the electronic properties of the organic thin films, and can be controlled by the substrate temperature during the vapor deposition. An optimal substrate temperature of 120 °C has been concluded to induced (221) molecular orientation over the (122) orientation and significantly improve the carrier transport of the SubPc thin film. A SubPc/C 60 heterojunction photovoltaic cells thus fabricated shows higher open-circuit voltage and up to 1.55% conversion efficiency has been achieved, which is attributed to preferential (221) orientation of the SubPc deposited at the elevated temperature.

Elevated Plasma Levels of Soluble (Pro)Renin Receptor in Patients with Obstructive Sleep Apnea Syndrome in Parallel with the Disease Severity.

Science.gov (United States)

Nishijima, Tsuguo; Tajima, Kazuki; Yamashiro, Yoshihiro; Hosokawa, Keisuke; Suwabe, Akira; Takahashi, Kazuhiro; Sakurai, Shigeru

2016-04-01

(Pro)renin receptor ((P)RR), a receptor for renin and prorenin, is implicated in the pathophysiology of diabetes mellitus, hypertension and their complications. Soluble (P)RR (s(P)RR) is composed of extracellular domain of (P)RR and thus exists in blood. We have reported that plasma concentrations of s(P)RR were elevated in male patients with obstructive sleep apnea syndrome (OSAS). The aim of the present study was to clarify the difference in plasma s(P)RR concentrations between male and female OSAS patients. Plasma s(P)RR concentrations were studied in 289 subjects (206 males and 83 females) consisting of 259 OSAS patients and 30 non-OSAS control subjects. The 259 OSAS patients were classified into mild (5 ≤ apnea hypopnea index (AHI) value found in male subjects (male r = 0.413, p < 0.0001; female r = 0.263, p < 0.05). Importantly, when OSAS patients (26 males and 15 females) with AHI ≥ 20 underwent continuous positive airway pressure treatment, plasma s(P)RR levels were significantly decreased. In conclusion, plasma s(P)RR levels are elevated in both male and female OSAS patients in parallel with the disease severity.

Varying patterns of the antihypertensive and antialbuminuric response to higher doses of renin-angiotensin-aldosterone system blockade in albuminuric hypertensive type 2 diabetes mellitus patients

DEFF Research Database (Denmark)

Weir, Matthew R; Hollenberg, Norman K; Remuzzi, Giuseppe

2011-01-01

In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction...

Effect of substrate on excess electrical conductivity in thin superconducting lead films above the transition temperature

Energy Technology Data Exchange (ETDEWEB)

Ashwini Kumar, P K

1976-03-01

Measurements were made on Pb films grown directly on to glass and Pb films grown on glass precoated with LiF to investigate the effect of the substrate on thermodynamic fluctuations of Cooper pairs. A change in the substrate appears to alter the strength of the pair breaking mechanism. 17 references.

Empirical evaluation of inhibitory product, substrate, and enzyme effects during the enzymatic saccharification of lignocellulosic biomass.

Science.gov (United States)

Smith, Benjamin T; Knutsen, Jeffrey S; Davis, Robert H

2010-05-01

The cellulose hydrolysis kinetics during batch enzymatic saccharification are typified by a rapid initial rate that subsequently decays, resulting in incomplete conversion. Previous studies suggest that changes associated with the solution, substrate, or enzymes may be responsible. In this work, kinetic experiments were conducted to determine the relative magnitude of these effects. Pretreated corn stover (PCS) was used as a lignocellulosic substrate likely to be found in a commercial saccharification process, while Avicel and Kraft lignin were used to create model substrates. Glucose inhibition was observed by spiking the reaction slurry with glucose during initial-rate experiments. Increasing the glucose concentration from 7 to 48 g/L reduced the cellulose conversion rate by 94%. When product sugars were removed using ultrafiltration with a 10 kDa membrane, the glucose-based conversion increased by 9.5%. Reductions in substrate reactivity with conversion were compared directly by saccharifying PCS and Avicel substrates that had been pre-reacted to different conversions. Reaction of substrate with a pre-conversion of 40% resulted in about 40% reduction in the initial rate of saccharification, relative to fresh substrate with identical cellulose concentration. Overall, glucose inhibition and reduced substrate reactivity appear to be dominant factors, whereas minimal reductions of enzyme activity were observed.

Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

Directory of Open Access Journals (Sweden)

Xia Zou

2015-01-01

Full Text Available Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN. Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF- β and α-smooth muscle action (SMA. Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05. Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

Effects of different needles and substrates on CuInS{sub 2} deposited by electrostatic spray deposition

Energy Technology Data Exchange (ETDEWEB)

Roncallo, S. [Centre for Materials Science and Engineering, Cranfield University, Shrivenham, Swindon, SN6 8LA (United Kingdom); Painter, J.D., E-mail: j.d.painter@cranfield.ac.u [Centre for Materials Science and Engineering, Cranfield University, Shrivenham, Swindon, SN6 8LA (United Kingdom); Healy, M.J.F. [Centre for Materials Science and Engineering, Cranfield University, Shrivenham, Swindon, SN6 8LA (United Kingdom); Ritchie, S.A.; Finnis, M.V. [Department of Engineering Systems and Management, Cranfield University, Shrivenham, Swindon SN6 8LA (United Kingdom); Rogers, K.D. [Cranfield Health, Cranfield University, Cranfield, Bedfordshire, MK43 0AL (United Kingdom); Scragg, J.J. [University of Bath, Claverton Down, Bath, BA2 7AY (United Kingdom); Dale, P.J. [Laboratoire Photovoltaique, University of Luxembourg, 41 Rue du Brill, L-4422, Belvaux (Luxembourg); Zoppi, G. [Northumbria Photovoltaics Applications Centre, Northumbria, University, Newcastle upon Tyne NE1 8ST (United Kingdom)

2011-03-31

Copper indium disulphide (CuInS{sub 2}) thin films were deposited using the electrostatic spray deposition method. The effects of applied voltage and solution flow rate on the aerosol cone shape, film composition, surface morphology and current conversion were investigated. The effect of aluminium substrates and transparent fluorine doped tin oxide (SnO{sub 2}:F) coated glass substrates on the properties of as-deposited CuInS{sub 2} films were analysed. An oxidation process occurs during the deposition onto the metallic substrates which forms an insulating layer between the photoactive film and substrate. The effects of two different spray needles on the properties of the as-deposited films were also studied. The results reveal that the use of a stainless steel needle results in contamination of the film due to the transfer of metal impurities through the spray whilst this is not seen for the glass needle. The films were characterised using a number of different analytical techniques such as X-ray diffraction, scanning electron microscopy, Rutherford back-scattering and secondary ion mass spectroscopy and opto-electronic measurements.

A Review of the Effect of Dietary Composition on Fasting Substrate Oxidation in Healthy and Overweight Subjects.

Science.gov (United States)

Whelan, Megan E; Wright, Olivia R L; Hickman, Ingrid J

2016-01-01

The purpose of this review was to assess existing evidence on the effects of chronic dietary macronutrient composition on substrate oxidation during a fasted state in healthy and overweight subjects. A systematic review of studies was conducted across five databases. Studies were included if they were English language studies of human adults, ≥19 years, used indirect calorimetry (ventilated hood technique), specified dietary macronutrient composition, and measured substrate oxidation. There was no evidence that variations of a typical, non-experimental diet influenced rate or ratio of substrate utilization, however there may be an upper and lower threshold for when macronutrient composition may directly alter preferences for fuel oxidation rates during a fasted state. This review indicates that macronutrient composition of a wide range of typical, non-experimental dietary fat and carbohydrate intakes has no effect on fasting substrate oxidation. This suggests that strict control of dietary intake prior to fasting indirect calorimetry measurements may be an unnecessary burden for study participants. Further research into the effects of long-term changes in isocaloric macronutrient shift is required.

Effect of Different Substrates and Casing Materials on the Growth and Yield of Calocybe indica.

Science.gov (United States)

Amin, Ruhul; Khair, Abul; Alam, Nuhu; Lee, Tae Soo

2010-06-01

Calocybe indica, a tropical edible mushroom, is popular because it has good nutritive value and it can be cultivated commercially. The current investigation was undertaken to determine a suitable substrate and the appropriate thickness of casing materials for the cultivation of C. indica. Optimum mycelial growth was observed in coconut coir substrate. Primordia initiation with the different substrates and casing materials was observed between the 13th and 19th day. The maximum length of stalk was recorded from sugarcane leaf, while diameter of stalk and pileus, and thickness of pileus were found in rice straw substrate. The highest biological and economic yield, and biological efficiency were also obtained in the rice straw substrate. Cow dung and loamy soil, farm-yard manure, loamy soil and sand, and spent oyster mushroom substrates were used as casing materials to evaluate the yield and yield-contributing characteristics of C. indica. The results indicate that the number of effective fruiting bodies, the biological and economic yield, and the biological efficiency were statistically similar all of the casing materials used. The maximum biological efficiency was found in the cow dung and loamy soil casing material. The cow dung and loamy soil (3 cm thick) was the best casing material and the rice straw was the best substrate for the commercial cultivation of C. indica.

Effects of the substrate temperature on the properties of CuIn{sub 5}S{sub 8} thin films

Energy Technology Data Exchange (ETDEWEB)

Gannouni, M., E-mail: gm_mounir@yahoo.fr [Laboratoire de Photovoltaique et Materiaux Semi-conducteurs - ENIT BP 37, Le belvedere 1002-Tunis (Tunisia); Kanzari, M. [Laboratoire de Photovoltaique et Materiaux Semi-conducteurs - ENIT BP 37, Le belvedere 1002-Tunis (Tunisia)

2011-10-01

Structural, optical and electrical properties of CuIn{sub 5}S{sub 8} thin films grown by thermal evaporation have been studied relating the effects of substrate heating conditions of these properties. The CuIn{sub 5}S{sub 8} thin films were carried out at substrate temperatures in the temperature range 100-300 deg. C. The effects of heated substrate on their physico-chemical properties were investigated using X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), optical transmission and hot probe method. X-ray diffraction revealed that the films are strong preferred orientation along the (3 1 1) plane upon substrate temperature 200 deg. C and amorphous for the substrate temperatures below 200 deg. C. No secondary phases are observed for all the films. The composition is greatly affected by heated substrate. From the optical transmission and reflection, an important absorption coefficient exceeds 10{sup 5} cm{sup -1} at 800 nm was found. As increasing the substrate temperature, the optical energy band gap decreases from 1.70 eV for the unheated films to 1.25 eV for the deposited films at 300 deg. C. It was found that CuIn{sub 5}S{sub 8} thin film is an n-type semiconductor at 250 deg. C.

8C.03: A KEY ROLE FOR ENDOTHELIN-1 IN THE PATHOGENESIS OF PREECLAMPSIA AND THE ASSOCIATED SUPPRESSION OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.

Science.gov (United States)

Verdonk, K; Saleh, L; Smilde, J E; van Ingen, M M; Garrelds, I M; Friesema, E C; Russcher, H; Steegers, E A P; van den Meiracker, A H; Visser, W; Danser, A H J

2015-06-01

Women with preeclampsia (PE) display low renin-angiotensin-aldosterone system (RAAS) activity and a high anti-angiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase-1(sFlt-1) and reduced levels of placental growth factor (PlGF). In the present study, we hypothesized that the RAAS suppression in PE is the consequence of the disturbed angiogenic balance. In a group of pregnant women with hypertensive disease of pregnancy and a group of healthy pregnant women, matched for gestational age (GA) we measured mean arterial blood pressure (MAP), urinary protein-to-creatinine ratio (PCR), and the plasma levels of sFlt-1, PlGF, albumin, creatinine, endothelin-1 (ET-1), renin (concentration and activity, PRC and PRA), angiotensinogen, and aldosterone. Since initial analysis revealed that these parameters strongly correlated with each other, multiple regression analysis was applied to establish independent determinants of ET-1, PRC, aldosterone and PCR. A sFlt-1/PlGF ratio >85 was considered to be representative for a high anti-angiogenic state. Of the 103 pregnant women included, 65 had a sFlt-1/PlGF ratio 85. Plasma ET-1 and creatinine levels were increased in women with a high ratio, whereas PRA and the plasma levels of renin, angiotensinogen, aldosterone and albumin were decreased in these women. The PRA-aldosterone relationship was identical in both groups. Multiple regression analysis revealed that PRC correlated independently with MAP and plasma ET-1 (R2 0.30). In turn, plasma ET-1 correlated positively with sFlt-1 and negatively with PRC (R2 0.52). Independent determinants of plasma aldosterone were GA and PRA (R2 0.56). Finally we found that plasma PlGF, plasma ET-1 and MAP determined PCR (R2 0.69). The high anti-angiogenic state in PE induces ET-1 activation. Together with the increased MAP in PE this factor suppresses renin release, and in parallel (via PRA reduction) aldosterone synthesis. The identical reduction in PRA and

Delayed addition of nitrogen-rich substrates during composting of municipal waste: Effects on nitrogen loss, greenhouse gas emissions and compost stability.

Science.gov (United States)

Nigussie, Abebe; Bruun, Sander; Kuyper, Thomas W; de Neergaard, Andreas

2017-01-01

Municipal waste is usually composted with an N-rich substrate, such as manure, to increase the N content of the product. This means that a significant amount of nitrogen can be lost during composting. The objectives of this study were (i) to investigate the effect of split addition of a nitrogen-rich substrate (poultry manure) on nitrogen losses and greenhouse gas emissions during composting and to link this effect to different bulking agents (coffee husks and sawdust), and (ii) to assess the effect of split addition of a nitrogen-rich substrate on compost stability and sanitisation. The results showed that split addition of the nitrogen-rich substrate reduced nitrogen losses by 9% when sawdust was used and 20% when coffee husks were used as the bulking agent. Depending on the bulking agent used, split addition increased cumulative N 2 O emissions by 400-600% compared to single addition. In contrast, single addition increased methane emissions by up to 50% compared to split addition of the substrate. Hence, the timing of the addition of the N-rich substrate had only a marginal effect on total non-CO 2 greenhouse gas emissions. Split addition of the N-rich substrate resulted in compost that was just as stable and effective at completely eradicating weed seeds as single addition. These findings therefore show that split addition of a nitrogen-rich substrate could be an option for increasing the fertilising value of municipal waste compost without having a significant effect on total greenhouse gas emissions or compost stability. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of the adsorbate layer on the work function reduction of gold substrates under external electric fields

Science.gov (United States)

He, Xiang; Cheng, Feng; Chen, Zhao-Xu

2017-12-01

The interface interaction between the dimethyl sulfide (DMS) molecule and the gold substrate under external electric fields is investigated by density functional theory method. The polarized DMS adsorbate reduces the work function of the gold substrate while the induced substrate dipole upon the adsorption slightly increases the work function. The DMS layer partially shields the Au(111) substrate from the electric fields and the vacuum level of DMS/Au(111) shifts less than of Au(111) in consequence. Under electric fields pointing outward from the Au(111) surface, both the reduction of work function and the adsorption of DMS molecule are enhanced on the surface. We also suggest the possible application of the field-effect transistor (FET) sensor with gold gate for detecting DMS molecule by utilizing the reduction of substrate work function upon adsorption. The effects of coverage and electric field on the theoretical sensitivity of the sensor are also discussed.

The Effect of Thermal Fluctuation on the Receptor-Mediated Adhesion of a Cell Membrane to an Elastic Substrate

Directory of Open Access Journals (Sweden)

Bahador Marzban

2017-04-01

Full Text Available Mechanics of the bilayer membrane play an important role in many biological and bioengineering problems such as cell–substrate and cell–nanomaterial interactions. In this work, we study the effect of thermal fluctuation and the substrate elasticity on the cell membrane–substrate adhesion. We model the adhesion of a fluctuating membrane on an elastic substrate as a two-step reaction comprised of the out-of-plane membrane fluctuation and the receptor–ligand binding. The equilibrium closed bond ratio as a function of substrate rigidity was computed by developing a coupled Fourier space Brownian dynamics and Monte Carlo method. The simulation results show that there exists a crossover value of the substrate rigidity at which the closed bond ratio is maximal.

The effect of body weight changes and endurance training on 24h substrate oxidation

NARCIS (Netherlands)

Pasman, W.J.; Westerterp-Plantenga, M.S.; Saris, W.H.M.

1999-01-01

The effect of body weight changes and endurance training on 24h substrate oxidation. Pasman WJ, Westerterp MS, Saris WH. Maastricht University, Department of Human Biology, The Netherlands. Pasman@voeding.tno.nl OBJECTIVE: To investigate the effect of exercise training and dietary macronutrient

Studying substrate effects on localized surface plasmons in an individual silver nanoparticle using electron energy-loss spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Fujiyoshi, Yoshifumi; Nemoto, Takashi; Kurata, Hiroki, E-mail: kurata@eels.kuicr.kyoto-u.ac.jp

2017-04-15

In this study, electron energy-loss spectroscopy (EELS) in conjunction with scanning transmission electron microscopy (STEM) was used to investigate surface plasmons in a single silver nanoparticle (NP) on a magnesium oxide substrate, employing an incident electron trajectory parallel to the substrate surface. This parallel irradiation allowed a direct exploration of the substrate effects on localized surface plasmon (LSP) excitations as a function of the distance from the substrate. The presence of the substrate was found to lower the symmetry of the system, such that the resonance energies of LSPs were dependent on the polarization direction relative to the substrate surface. The resulting mode splitting could be detected by applying different electron trajectories, providing results similar to those previously obtained from optical studies using polarized light. However, the LSP maps obtained by STEM-EELS analysis show an asymmetric intensity distribution with the highest intensity at the top surface of the NP (that is, far from the substrate), a result that is not predicted by optical simulations. We show that modifications of the applied electric field by the substrate cause this asymmetric intensity distribution in the LSP maps.

Effects of adhesion dynamics and substrate compliance on the shape and motility of crawling cells.

Directory of Open Access Journals (Sweden)

Falko Ziebert

Full Text Available Computational modeling of eukaryotic cells moving on substrates is an extraordinarily complex task: many physical processes, such as actin polymerization, action of motors, formation of adhesive contacts concomitant with both substrate deformation and recruitment of actin etc., as well as regulatory pathways are intertwined. Moreover, highly nontrivial cell responses emerge when the substrate becomes deformable and/or heterogeneous. Here we extended a computational model for motile cell fragments, based on an earlier developed phase field approach, to account for explicit dynamics of adhesion site formation, as well as for substrate compliance via an effective elastic spring. Our model displays steady motion vs. stick-slip transitions with concomitant shape oscillations as a function of the actin protrusion rate, the substrate stiffness, and the rates of adhesion. Implementing a step in the substrate's elastic modulus, as well as periodic patterned surfaces exemplified by alternating stripes of high and low adhesiveness, we were able to reproduce the correct motility modes and shape phenomenology found experimentally. We also predict the following nontrivial behavior: the direction of motion of cells can switch from parallel to perpendicular to the stripes as a function of both the adhesion strength and the width ratio of adhesive to non-adhesive stripes.

Effect of flow velocity, substrate concentration and hydraulic cleaning on biofouling of reverse osmosis feed channels

KAUST Repository

Radu, Andrea I.

2012-04-01

A two-dimensional mathematical model coupling fluid dynamics, salt and substrate transport and biofilm development in time was used to investigate the effects of cross-flow velocity and substrate availability on biofouling in reverse osmosis (RO)/nanofiltration (NF) feed channels. Simulations performed in channels with or without spacer filaments describe how higher liquid velocities lead to less overall biomass amount in the channel by increasing the shear stress. In all studied cases at constant feed flow rate, biomass accumulation in the channel reached a steady state. Replicate simulation runs prove that the stochastic biomass attachment model does not affect the stationary biomass level achieved and has only a slight influence on the dynamics of biomass accumulation. Biofilm removal strategies based on velocity variations are evaluated. Numerical results indicate that sudden velocity increase could lead to biomass sloughing, followed however by biomass re-growth when returning to initial operating conditions. Simulations show particularities of substrate availability in membrane devices used for water treatment, e.g., the accumulation of rejected substrates at the membrane surface due to concentration polarization. Interestingly, with an increased biofilm thickness, the overall substrate consumption rate dominates over accumulation due to substrate concentration polarization, eventually leading to decreased substrate concentrations in the biofilm compared to bulk liquid. © 2012 Elsevier B.V.

Thermal Effect of Ceramic Substrate on Heat Distribution in Thermoelectric Generators

DEFF Research Database (Denmark)

Kolaei, Alireza Rezania; Rosendahl, Lasse

2012-01-01

in the heat sink, a parallel microchannel heat sink is applied to a real TEG. The focus of this study is a discussion of the temperature difference variation between the cold/hot sides of the TEG legs versus the variation of the thermal conductivity of the ceramic substrate and the thickness of the substrate...... that the temperature difference is affected remarkably by the pressure drops in the heat sink, the thermal conductivity of the ceramic substrate, and the thickness of the substrate on the hot side....

In vitro fermentation of total mixed diets differing in concentrate proportion: relative effects of inocula and substrates.

Science.gov (United States)

Serment, Amélie; Giger-Reverdin, Sylvie; Schmidely, Philippe; Dhumez, Ophélie; Broudiscou, Laurent P; Sauvant, Daniel

2016-01-15

In vitro techniques are used to predict ruminant feedstuff values or characterise rumen fermentation. As the results are influenced by several factors, such as the relative effects of inocula and substrates, this study aimed to examine in vitro incubation of two total mixed rations (substrates) differing in their proportion of concentrate [low (L): 350 g kg(-1) vs. high (H): 700 g kg(-1)] incubated in inocula provided by goats fed either a L or a H diet. Gas production and composition in carbon dioxide (CO2), methane (CH4 ) and hydrogen (H2), volatile fatty acids (VFAs), soluble carbohydrates (SCs) and ammonia (NH3) concentrations, and pH of the fermentation fluid were measured. In comparison with the L inoculum and L substrate, the H ones produced more CO2 and CH4 gas, which led to higher SCs and VFA concentrations, and lower acetate-to-propionate ratio and NH3 concentration, with a predominant effect of the inoculum. The effects of the inocula and of the substrates were additive using donor animals adapted to the diets. © 2015 Society of Chemical Industry.

Substrate Effect on Carbon/Ceramic Mixed Matrix Membrane Prepared by a Vacuum-Assisted Method for Desalination

Directory of Open Access Journals (Sweden)

Yingjun Song

2018-05-01

Full Text Available This work investigates the effect of various membrane substrates and coating conditions on the formation of carbon/ceramic mixed matrix membranes for desalination application. The substrates were impregnated with phenolic resin via a vacuum-assisted method followed by carbonization under an inert gas. Substrates with pore sizes of 100 nm required a single impregnation step only, where short vacuum times (<120 s resulted in low quality membranes with defects. For vacuum times of ≥120 s, high quality membranes with homogeneous impregnation were prepared leading to high salt rejection (>90% and high water fluxes (up to 25 L m−2 h−1. The increase in water flux as a function of the vacuum time confirms the vacuum etching effect resulting from the vacuum-assisted method. Substrates with pore sizes of 140 nm required two impregnation steps. These pores were too large for the ceramic inter-particle space to be filled with phenolic resin via a single step. In the second impregnation step, increasing the concentration of the phenolic resin resulted in membranes with lower water fluxes. These results indicate that thicker films were formed by increasing the phenolic resin concentration. In the case of substrates with pores of 600 nm, these pores were too large and inter-particle space filling with phenolic resin was not attained.

Effect of Feed Substrate Thickness on the Bandwidth and Radiation Characteristics of an Aperture-Coupled Microstrip Antenna with a High Permittivity Feed Substrate

Directory of Open Access Journals (Sweden)

Jae-Hyun Kim

2018-04-01

Full Text Available The impedance bandwidth and radiation characteristics of an aperture-coupled microstrip line-fed patch antenna (ACMPA with a high permittivity (ɛr = 10 feed substrate suitable for integration with a monolithic microwave integrated circuit (MMIC are investigated for various feed substrate thicknesses through an experiment and computer simulation. The impedance bandwidth of an ACMPA with a high permittivity feed substrate increases as the feed substrate thickness decreases. Furthermore, the front-to-back ratio of an ACMPA with a high permittivity feed substrate increases and the cross-polarization level decreases as the feed substrate thickness decreases. As the impedance bandwidth of an ACMPA with a high permittivity feed substrate increases and its radiation characteristics improve as the feed substrate thickness decreases, the ACMPA configuration becomes suitable for integration with an MMIC.

QTES-DFTB dynamics study on the effect of substrate motion on quantum proton transfer in soybean lipoxygenase-1

Science.gov (United States)

Mazzuca, James; Garashchuk, Sophya; Jakowski, Jacek

2014-03-01

It has been shown that the proton transfer in the enzymatic active site of soybean lipoxygenase-1 (SLO-1) occurs largely by a quantum tunneling mechanism. This study examined the role of local substrate vibrations on this proton tunneling reaction. We employ an approximate quantum trajectory (QT) dynamics method with linear quantum force. The electronic structure (ES) was calculated on-the-fly with a density functional tight binding (DFTB) method. This QTES-DFTB method scales linearly with number of trajectories, and the calculation of the quantum force is a small addition to the overall cost of trajectory dynamics. The active site was represented as a 44-atom system. Quantum effects were included only for the transferring proton, and substrate nuclei were treated classically. The effect of substrate vibrations was evaluated by freezing or relaxing the substrate nuclei. Trajectory calculations were performed at several temperatures ranging from 250-350 K, and rate constants were calculated through the quantum mechanical flux operator which depends on time-dependent correlation functions. It was found that the substrate motion reliably increases the rate constants, as well as the P/D kinetic isotope effect, by approximately 10% across all temperatures examined. NSF Grant No. CHE-1056188, APRA-NSF-EPS-0919436, and CHE-1048629, NICS Teragrid/Xsede TG-DMR110037.

The Effect of Substrate-Bulk Interaction on Hydrolysis Modeling in Anaerobic Digestion Process

Directory of Open Access Journals (Sweden)

Antonio Panico

2014-11-01

Full Text Available In an Anaerobic Digestion (AD process treating particulate substrates, the size of solids is expected to negatively affect the rate of hydrolysis step and consequently influence the performance of the whole process. To avoid any disadvantage due to size of solids, expensive pre-treatments aimed at disintegrating and solubilizing substrates are commonly conducted prior to AD. This practice is doubtlessly successful, but not always necessary, since some organic substrates, although particulate, once immersed in water, tend to solubilize immediately. This aspect, if properly considered, could result in saving money and time in the AD process, as well as refining the development and calibration of AD mathematical models. The present study is actually aimed at demonstrating, through experiments and mathematical simulations, different results deriving from the AD process performed, under the same operating conditions, on two different substrates, i.e. homemade pasta and carrot batons, having the same particle size, but different chemical composition and texture. Experimental outcomes highlighted the effect of particles size on bio-methane production only from the bio-methanation potential tests (BMP conducted on carrot batons. Similar results were obtained by mathematical model calibration, i.e., different kinetic constants for differently-sized carrot batons and same kinetic constant for differently-sized homemade pasta solids.

The physiology of a local renin-angiotensin system in the pancreas.

Science.gov (United States)

Leung, Po Sing

2007-04-01

The systemic renin-angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the expression of which is modulated in response to physiological and pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation, hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to have important endocrine and exocrine roles in the pancreas, regulating local blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme secretion, islet beta-cell (pro)insulin biosynthesis, and thus, glucose-stimulated insulin release, delta-cell somatostatin secretion, and pancreatic cell proliferation and differentiation. It may further mediate oxidative stress-induced cell inflammation, apoptosis and fibrosis. Further exploration of this system would probably offer new insights into the pathogenesis of pancreatitis, diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic targets and strategies might thus be suggested.

Effects of polydeoxyribonucleotides (PDRN) on wound healing: Electric cell-substrate impedance sensing (ECIS)

Energy Technology Data Exchange (ETDEWEB)

Koo, Youngmi; Yun, Yeoheung, E-mail: yyun@ncat.edu

2016-12-01

Polydeoxyribonucleotides (PDRN) have been explored as an effective treatment for tissue repair in peripheral artery occlusive disease, diabetic foot ulcers, and eye lotion. We report on the effect of polydeoxyribonucleotides (PDRN) on wound healing by using the electric cell-substrate impedance sensing (ECIS) system and viability testing. Human osteoblasts (U2OS) and primary human dermal fibroblasts (HDF) were used to study the effect of PDRN on migration and proliferation. ECIS allowed the creation of a wound by applying high current, and then monitoring the healing process by measuring impedance in real time. The traditional culture-insert gap-closure migration assay was performed and compared with the ECIS wound assay. PDRN-treated U2OS and HDF cells affected cell motilities to wounding site. Viability test results show that HDF and U2OS proliferation depended on PDRN concentration. Based on the results, a PDRN compound can be useful in wound healing associated with bone and skin. - Highlights: • Wound-healing study by the electric cell-substrate impedance sensing (ECIS). • Effect of polydeoxyribonucleotides (PDRN) on migration and proliferation of U2OS and HDF. • Effect of PDRN concentration on viability of U2OS and HDF.

Effects of polydeoxyribonucleotides (PDRN) on wound healing: Electric cell-substrate impedance sensing (ECIS)

International Nuclear Information System (INIS)

Koo, Youngmi; Yun, Yeoheung

2016-01-01

Polydeoxyribonucleotides (PDRN) have been explored as an effective treatment for tissue repair in peripheral artery occlusive disease, diabetic foot ulcers, and eye lotion. We report on the effect of polydeoxyribonucleotides (PDRN) on wound healing by using the electric cell-substrate impedance sensing (ECIS) system and viability testing. Human osteoblasts (U2OS) and primary human dermal fibroblasts (HDF) were used to study the effect of PDRN on migration and proliferation. ECIS allowed the creation of a wound by applying high current, and then monitoring the healing process by measuring impedance in real time. The traditional culture-insert gap-closure migration assay was performed and compared with the ECIS wound assay. PDRN-treated U2OS and HDF cells affected cell motilities to wounding site. Viability test results show that HDF and U2OS proliferation depended on PDRN concentration. Based on the results, a PDRN compound can be useful in wound healing associated with bone and skin. - Highlights: • Wound-healing study by the electric cell-substrate impedance sensing (ECIS). • Effect of polydeoxyribonucleotides (PDRN) on migration and proliferation of U2OS and HDF. • Effect of PDRN concentration on viability of U2OS and HDF.

Substrate optimization for integrated circuit antennas

OpenAIRE

Alexopoulos, N. G.; Katehi, P. B.; Rutledge, D. B.

1982-01-01

Imaging systems in microwaves, millimeter and submillimeter wave applications employ printed circuit antenna elements. The effect of substrate properties is analyzed in this paper by both reciprocity theorem as well as integral equation approach for infinitesimally short as well as finite length dipole and slot elements. Radiation efficiency and substrate surface wave guidance is studied for practical substrate materials as GaAs, Silicon, Quartz and Duroid.

Effects of substrate preheating during direct energy deposition on microstructure, hardness, tensile strength, and notch toughness

Science.gov (United States)

Baek, Gyeong Yun; Lee, Ki Yong; Park, Sang Hu; Shim, Do Sik

2017-11-01

This study examined the effects of substrate preheating for the hardfacing of cold-press dies using the high-speed tool steel AISI M4. The preheating of the substrate is a widely used technique for reducing the degree of thermal deformation and preventing crack formation. We investigated the changes in the metallurgical and mechanical properties of the high-speed tool steel M4 deposited on an AISI D2 substrate with changes in the substrate preheating temperature. Five preheating temperatures (100-500 °C; interval of 100 °C) were selected, and the changes in the temperature of the substrate during deposition were observed. As the preheating temperature of the substrate was increased, the temperature gradient between the melting layer and the substrate decreased; this prevented the formation of internal cracks, owing to thermal stress relief. Field-emission scanning electron microscopy showed that a dendritic structure was formed at the interface between the deposited layer and the substrate while a cellular microstructure was formed in the deposited layer. As the preheating temperature was increased, the sizes of the cells and precipitated carbides also increased. Furthermore, the hardness increased slightly while the strength and toughness decreased. Moreover, the tensile and impact properties deteriorated rapidly at excessively high preheating temperatures (greater than 500 °C). The results of this study can be used as preheating criteria for achieving the desired mechanical properties during the hardfacing of dies and molds.

[Differences of blood plasma renin activity, angiotensin II and aldosterone levels in essential or secondary hypertension].

Science.gov (United States)

Song, Ai-ling; Zeng, Zheng-pei; Tong, An-li; Lu, Lin; Chen, Shi; Li, Ming; Fu, Chun-li; Wang, Yong-hui; Sun, Mei-li

2012-04-01

To study on the difference of plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO), and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR). The plasma aldosterone, Ang II and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA, n = 111), aldosterone-producing adenoma (APA, n = 118), PHEO (n = 98) and EH (n = 86). ARR was calculated. Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [374 (294, 465) pmol/L and 629 (449, 997) pmol/L] and PA group [471 (346, 632) pmol/L and 673 (499, 825) pmol/L] were higher than those in EH group [277 (224, 332) pmol/L and 427 (341, 501) pmol/L] (P 0.05). The PRA level in both positions of each group were PHEO group [0.3 (0.2, 1.0) µg · L(-1) · h(-1) and 1.4 (0.6, 3.4) µg · L(-1) · h(-1)] > EH group [0.2 (0.1, 0.4) µg · L(-1) · h(-1) and 0.6 (0.4, 1.0) µg · L(-1) · h(-1)] (P PA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (P < 0.01), and APA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.1 (0.1, 0.3) µg · L(-1) · h(-1)] < IHA group [0.1 (0.1, 0.2) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (supine P < 0.01; upright P < 0.05). APA was divided into 2 types with renin-Ang II-responsive APA (n = 26) and unresponsive APA (n = 92). The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang II-responsive APA than in unresponsive APA patients. ARR in upright was higher in PA group (P < 0.01) but lower in PHEO group (P < 0.05) compared with EH. ARR was higher in APA than in IHA (P < 0.01). The sensitivity and specificity of ARR as 40 (aldosterone unit: ng/dl; PRA unit: µg · L(-1

Iridium Coating Deposited by Double Glow Plasma Technique — Effect of Glow Plasma on Structure of Coating at Single Substrate Edge

International Nuclear Information System (INIS)

Wu Wangping; Chen Zhaofeng; Liu Yong

2012-01-01

Double glow plasma technique has a high deposition rate for preparing iridium coating. However, the glow plasma can influence the structure of the coating at the single substrate edge. In this study, the iridium coating was prepared by double glow plasma on the surface of single niobium substrate. The microstructure of iridium coating at the substrate edge was observed by scanning electron microscopy. The composition of the coating was confirmed by energy dispersive spectroscopy and X-ray diffraction. There was a boundary between the coating and the substrate edge. The covered area for the iridium coating at the substrate edge became fewer and fewer from the inner area to the outer flange-area. The bamboo sprout-like particles on the surface of the substrate edge were composed of elemental niobium. The substrate edge was composed of the Nb coating and there was a transition zone between the Ir coating and the Nb coating. The interesting phenomenon of the substrate edge could be attributed to the effects of the bias voltages and the plasma cloud in the deposition chamber. The substrate edge effect could be mitigated or eliminated by adding lots of small niobium plates around the substrate in a deposition process. (plasma technology)

The effect of micro-ECoG substrate footprint on the meningeal tissue response

Science.gov (United States)

Schendel, Amelia A.; Nonte, Michael W.; Vokoun, Corinne; Richner, Thomas J.; Brodnick, Sarah K.; Atry, Farid; Frye, Seth; Bostrom, Paige; Pashaie, Ramin; Thongpang, Sanitta; Eliceiri, Kevin W.; Williams, Justin C.

2014-08-01

Objective. There is great interest in designing implantable neural electrode arrays that maximize function while minimizing tissue effects and damage. Although it has been shown that substrate geometry plays a key role in the tissue response to intracortically implanted, penetrating neural interfaces, there has been minimal investigation into the effect of substrate footprint on the tissue response to surface electrode arrays. This study investigates the effect of micro-electrocorticography (micro-ECoG) device geometry on the longitudinal tissue response. Approach. The meningeal tissue response to two micro-ECoG devices with differing geometries was evaluated. The first device had each electrode site and trace individually insulated, with open regions in between, while the second device had a solid substrate, in which all 16 electrode sites were embedded in a continuous insulating sheet. These devices were implanted bilaterally in rats, beneath cranial windows, through which the meningeal tissue response was monitored for one month after implantation. Electrode site impedance spectra were also monitored during the implantation period. Main results. It was observed that collagenous scar tissue formed around both types of devices. However, the distribution of the tissue growth was different between the two array designs. The mesh devices experienced thick tissue growth between the device and the cranial window, and minimal tissue growth between the device and the brain, while the solid device showed the opposite effect, with thick tissue forming between the brain and the electrode sites. Significance. These data suggest that an open architecture device would be more ideal for neural recording applications, in which a low impedance path from the brain to the electrode sites is critical for maximum recording quality.

Effect of substrate porosity on photoluminescence properties of ZnS films prepared on porous Si substrates by pulsed laser deposition

Science.gov (United States)

Wang, Cai-Feng; Li, Qing-Shan; Zhang, Li-Chun; Lv, Lei; Qi, Hong-Xia

2007-05-01

ZnS films were deposited on porous Si (PS) substrates with different porosities by pulsed laser deposition. The photoluminescence spectra of the samples were measured to study the effect of substrate porosity on luminescence properties of ZnS/porous Si composites. After deposition of ZnS films, the red photoluminescence peak of porous Si shows a slight blueshift compared with as-prepared porous Si samples. With an increase of the porosity, a green emission at about 550 nm was observed which may be ascribed to the defect-center luminescence of ZnS films, and the photoluminescence of ZnS/porous Si composites is very close to white light. Good crystal structures of the samples were observed by x-ray diffraction, showing that ZnS films were grown in preferred orientation. Due to the roughness of porous Si surface, some cracks appear in ZnS films, which could be seen from scanning electron microscope images.

Effects of RF plasma treatment on spray-pyrolyzed copper oxide films on silicon substrates

Science.gov (United States)

Madera, Rozen Grace B.; Martinez, Melanie M.; Vasquez, Magdaleno R., Jr.

2018-01-01

The effects of radio-frequency (RF) argon (Ar) plasma treatment on the structural, morphological, electrical and compositional properties of the spray-pyrolyzed p-type copper oxide films on n-type (100) silicon (Si) substrates were investigated. The films were successfully synthesized using 0.3 M copper acetate monohydrate sprayed on precut Si substrates maintained at 350 °C. X-ray diffraction revealed cupric oxide (CuO) with a monoclinic structure. An apparent improvement in crystallinity was realized after Ar plasma treatment, attributed to the removal of residues contaminating the surface. Scanning electron microscope images showed agglomerated monoclinic grains and revealed a reduction in size upon plasma exposure induced by the sputtering effect. The current-voltage characteristics of CuO/Si showed a rectifying behavior after Ar plasma exposure with an increase in turn-on voltage. Four-point probe measurements revealed a decrease in sheet resistance after plasma irradiation. Fourier transform infrared spectral analyses also showed O-H and C-O bands on the films. This work was able to produce CuO thin films via spray pyrolysis on Si substrates and enhancement in their properties by applying postdeposition Ar plasma treatment.

Plastic properties of thin films on substrates as measured by submicron indentation hardness and substrate curvature techniques

International Nuclear Information System (INIS)

Doerner, M.F.; Gardner, D.S.; Nix, W.D.

1986-01-01

Substrate curvature and submicron indentation measurements have been used recently to study plastic deformation in thin films on substrates. In the present work both of these techniques have been employed to study the strength of aluminum and tungsten thin films on silicon substrates. In the case of aluminum films on silicon substrates, the film strength is found to increase with decreasing thickness. Grain size variations with film thickness do not account for the variations in strength. Wafer curvature measurements give strengths higher than those predicted from hardness measurements suggesting the substrate plays a role in strengthening the film. The observed strengthening effect with decreased thickness may be due to image forces on dislocations in the film due to the elastically stiffer silicon substrate. For sputtered tungsten films, where the substrate is less stiff than the film, the film strength decreases with decreasing film thickness

Biohydrogen production from rotten orange with immobilized mixed culture: Effect of immobilization media for various composition of substrates

Energy Technology Data Exchange (ETDEWEB)

Damayanti, Astrilia, E-mail: liasholehasd@gmail.com [Department of Chemical Engineering, Faculty of Engineering, Semarang State University, E1 Building, 2nd floor, Kampus Sekaran, Gunungpati, Semarang 50229 (Indonesia); Department of Chemical Engineering, Faculty of Engineering, Gadjah Mada University, Jl. Grafika No. 2, Kampus UGM, Yogyakarta 55281 (Indonesia); Sarto,; Syamsiah, Siti; Sediawan, Wahyudi B. [Department of Chemical Engineering, Faculty of Engineering, Gadjah Mada University, Jl. Grafika No. 2, Kampus UGM, Yogyakarta 55281 (Indonesia)

2015-12-29

Enriched–immobilized mixed culture was utilized to produce biohydrogen in mesophilic condition under anaerobic condition using rotten orange as substrate. The process was conducted in batch reactors for 100 hours. Microbial cultures from three different sources were subject to a series of enrichment and immobilized in two different types of media, i.e. calcium alginate (CA, 2%) and mixture of alginate and activated carbon (CAC, 1:1). The performance of immobilized culture in each media was tested for biohydrogen production using four different substrate compositions, namely orange meat (OM), orange meat added with peel (OMP), orange meat added with limonene (OML), and mixture of orange meat and peel added with limonene (OMPL). The results show that, with immobilized culture in CA, the variation of substrate composition gave significant effect on the production of biohydrogen. The highest production of biohydrogen was detected for substrate containing only orange meet, i.e. 2.5%, which was about 3-5 times higher than biohydrogen production from other compositions of substrate. The use of immobilized culture in CAC in general has increased the hydrogen production by 2-7 times depending on the composition of substrate, i.e. 5.4%, 4.8%, 5.1%, and 4.4% for OM, OMP, OML, and OMPL, respectively. The addition of activated carbon has eliminated the effect of inhibitory compounds in the substrate. The major soluble metabolites were acetic acid, propionic acid, and butyric acid.

Biohydrogen production from rotten orange with immobilized mixed culture: Effect of immobilization media for various composition of substrates

Science.gov (United States)

Damayanti, Astrilia; Sarto, Syamsiah, Siti; Sediawan, Wahyudi B.

2015-12-01

Enriched-immobilized mixed culture was utilized to produce biohydrogen in mesophilic condition under anaerobic condition using rotten orange as substrate. The process was conducted in batch reactors for 100 hours. Microbial cultures from three different sources were subject to a series of enrichment and immobilized in two different types of media, i.e. calcium alginate (CA, 2%) and mixture of alginate and activated carbon (CAC, 1:1). The performance of immobilized culture in each media was tested for biohydrogen production using four different substrate compositions, namely orange meat (OM), orange meat added with peel (OMP), orange meat added with limonene (OML), and mixture of orange meat and peel added with limonene (OMPL). The results show that, with immobilized culture in CA, the variation of substrate composition gave significant effect on the production of biohydrogen. The highest production of biohydrogen was detected for substrate containing only orange meet, i.e. 2.5%, which was about 3-5 times higher than biohydrogen production from other compositions of substrate. The use of immobilized culture in CAC in general has increased the hydrogen production by 2-7 times depending on the composition of substrate, i.e. 5.4%, 4.8%, 5.1%, and 4.4% for OM, OMP, OML, and OMPL, respectively. The addition of activated carbon has eliminated the effect of inhibitory compounds in the substrate. The major soluble metabolites were acetic acid, propionic acid, and butyric acid.

Biohydrogen production from rotten orange with immobilized mixed culture: Effect of immobilization media for various composition of substrates

International Nuclear Information System (INIS)

Damayanti, Astrilia; Sarto,; Syamsiah, Siti; Sediawan, Wahyudi B.

2015-01-01

Enriched–immobilized mixed culture was utilized to produce biohydrogen in mesophilic condition under anaerobic condition using rotten orange as substrate. The process was conducted in batch reactors for 100 hours. Microbial cultures from three different sources were subject to a series of enrichment and immobilized in two different types of media, i.e. calcium alginate (CA, 2%) and mixture of alginate and activated carbon (CAC, 1:1). The performance of immobilized culture in each media was tested for biohydrogen production using four different substrate compositions, namely orange meat (OM), orange meat added with peel (OMP), orange meat added with limonene (OML), and mixture of orange meat and peel added with limonene (OMPL). The results show that, with immobilized culture in CA, the variation of substrate composition gave significant effect on the production of biohydrogen. The highest production of biohydrogen was detected for substrate containing only orange meet, i.e. 2.5%, which was about 3-5 times higher than biohydrogen production from other compositions of substrate. The use of immobilized culture in CAC in general has increased the hydrogen production by 2-7 times depending on the composition of substrate, i.e. 5.4%, 4.8%, 5.1%, and 4.4% for OM, OMP, OML, and OMPL, respectively. The addition of activated carbon has eliminated the effect of inhibitory compounds in the substrate. The major soluble metabolites were acetic acid, propionic acid, and butyric acid

Silver Nanoparticle-Decorated Shape-Memory Polystyrene Sheets as Highly Sensitive Surface-Enhanced Raman Scattering Substrates with a Thermally Inducible Hot Spot Effect.

Science.gov (United States)

Mengesha, Zebasil Tassew; Yang, Jyisy

2016-11-15

In this study, an active surface-enhanced Raman scattering (SERS) substrate with a thermally inducible hot spot effect for sensitive measurement of Raman-active molecules was successfully fabricated from silver nanoparticle (AgNP)-decorated shape-memory polystyrene (SMP) sheets. To prepare the SERS substrate, SMP sheets were first pretreated with n-octylamine for effective decoration with AgNPs. By varying the formulation and condition of the reduction reaction, AgNP-decorated SMP (Ag@SMP) substrates were successfully prepared with optimized particle gaps to produce inducible hot spot effects on thermal shrink. High-quality SERS spectra were easily obtained with enhancement factors higher than 10 8 by probing with aromatic thiols. Several Ag@SMP substrates produced under different reaction conditions were explored for the creation of inducible hot spot effects. The results indicated that AgNP spacing is crucial for strong hot spot effects. The suitability of Ag@SMP substrates for quantification was also evaluated according to the detection of adenine. Results confirmed that prepared Ag@SMP substrates were highly suitable for quantitative analysis because they yielded an estimated limit of detection as low as 120 pg/cm 2 , a linear range of up to 7 ng/cm 2 , and a regression coefficient (R 2 ) of 0.9959. Ag@SMP substrates were highly reproducible; the average relative standard deviation for all measurements was less than 10%.

Renin-angiotensin system blockade therapy after transcatheter aortic valve implantation.

Science.gov (United States)

Ochiai, Tomoki; Saito, Shigeru; Yamanaka, Futoshi; Shishido, Koki; Tanaka, Yutaka; Yamabe, Tsuyoshi; Shirai, Shinichi; Tada, Norio; Araki, Motoharu; Naganuma, Toru; Watanabe, Yusuke; Yamamoto, Masanori; Hayashida, Kentaro

2018-04-01

The persistence of left ventricular (LV) hypertrophy is associated with poor clinical outcomes after transcatheter aortic valve implantation (TAVI) for aortic stenosis. However, the optimal medical therapy after TAVI remains unknown. We investigated the effect of renin-angiotensin system (RAS) blockade therapy on LV hypertrophy and mortality in patients undergoing TAVI. Between October 2013 and April 2016, 1215 patients undergoing TAVI were prospectively enrolled in the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI registry. This cohort was stratified according to the postoperative usage of RAS blockade therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Patients with at least two prescriptions dispensed 180 days apart after TAVI and at least a 6-month follow-up constituted the RAS blockade group (n=371), while those not prescribed any ACE inhibitors or ARBs after TAVI were included in the no RAS blockade group (n=189). At 6 months postoperatively, the RAS blockade group had significantly greater LV mass index regression than the no RAS blockade group (-9±24% vs -2±25%, p=0.024). Kaplan-Meier analysis revealed a significantly lower cumulative 2-year mortality in the RAS blockade than that in the no RAS blockade group (7.5% vs 12.5%; log-rank test, p=0.031). After adjusting for confounding factors, RAS blockade therapy was associated with significantly lower all-cause mortality (HR, 0.45; 95% CI 0.22 to 0.91; p=0.025). Postoperative RAS blockade therapy is associated with greater LV mass index regression and reduced all-cause mortality. These data need to be confirmed by a prospective randomised controlled outcome trial. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of UV Aging on the Cracking of Titanium Oxide Layer on Poly(ethylene terephthalate) Substrate: Preprint

Energy Technology Data Exchange (ETDEWEB)

Zhang, Chao; Gray, Matthew H.; Tirawat, Robert; Larsen, Ross E.; Chen, Fangliang

2016-04-18

Thin oxide and metal films deposited on polymer substrates is an emerging technology for advanced reflectors for concentrated solar power applications, due to their unique combination of light weight, flexibility and inexpensive manufacture. Thus far, there is little knowledge on the mechanical integrity or structural persistence of such multi-layer thin film systems under long-term environmental aging. In this paper, the cracking of a brittle titanium dioxide layer deposited onto elasto-plastic poly(ethylene terephthalate) (PET) substrate is studied through a combination of experiment and modeling. In-situ fragmentation tests have been conducted to monitor the onset and evolution of cracks both on pristine and on samples aged with ultraviolet (UV) light. An analytical model is presented to simulate the cracking behavior and to predict the effects of UV aging. Based on preliminary experimental observation, the effect of aging is divided into three aspects and analyzed independently: mechanical property degradation of the polymer substrate; degradation of the interlayer between substrate and oxide coating; and internal stress-induced cracks on the oxide coating.

Living high training low induces physiological cardiac hypertrophy accompanied by down-regulation and redistribution of the renin-angiotensin system

Science.gov (United States)

Shi, Wei; Meszaros, J Gary; Zeng, Shao-ju; Sun, Ying-yu; Zuo, Ming-xue

2013-01-01

Aim: Living high training low” (LHTL) is an exercise-training protocol that refers living in hypoxia stress and training at normal level of O2. In this study, we investigated whether LHTL caused physiological heart hypertrophy accompanied by changes of biomarkers in renin-angiotensin system in rats. Methods: Adult male SD rats were randomly assigned into 4 groups, and trained on living low-sedentary (LLS, control), living low-training low (LLTL), living high-sedentary (LHS) and living high-training low (LHTL) protocols, respectively, for 4 weeks. Hematological parameters, hemodynamic measurement, heart hypertrophy and plasma angiotensin II (Ang II) level of the rats were measured. The gene and protein expression of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II receptor I (AT1) in heart tissue was assessed using RT-PCR and immunohistochemistry, respectively. Results: LLTL, LHS and LHTL significantly improved cardiac function, increased hemoglobin concentration and RBC. At the molecular level, LLTL, LHS and LHTL significantly decreased the expression of ACE, AGT and AT1 genes, but increased the expression of ACE and AT1 proteins in heart tissue. Moreover, ACE and AT1 protein expression was significantly increased in the endocardium, but unchanged in the epicardium. Conclusion: LHTL training protocol suppresses ACE, AGT and AT1 gene expression in heart tissue, but increases ACE and AT1 protein expression specifically in the endocardium, suggesting that the physiological heart hypertrophy induced by LHTL is regulated by region-specific expression of renin-angiotensin system components. PMID:23377552

Multifunctionality is affected by interactions between green roof plant species, substrate depth, and substrate type.

Science.gov (United States)

Dusza, Yann; Barot, Sébastien; Kraepiel, Yvan; Lata, Jean-Christophe; Abbadie, Luc; Raynaud, Xavier

2017-04-01

Green roofs provide ecosystem services through evapotranspiration and nutrient cycling that depend, among others, on plant species, substrate type, and substrate depth. However, no study has assessed thoroughly how interactions between these factors alter ecosystem functions and multifunctionality of green roofs. We simulated some green roof conditions in a pot experiment. We planted 20 plant species from 10 genera and five families (Asteraceae, Caryophyllaceae, Crassulaceae, Fabaceae, and Poaceae) on two substrate types (natural vs. artificial) and two substrate depths (10 cm vs. 30 cm). As indicators of major ecosystem functions, we measured aboveground and belowground biomasses, foliar nitrogen and carbon content, foliar transpiration, substrate water retention, and dissolved organic carbon and nitrates in leachates. Interactions between substrate type and depth strongly affected ecosystem functions. Biomass production was increased in the artificial substrate and deeper substrates, as was water retention in most cases. In contrast, dissolved organic carbon leaching was higher in the artificial substrates. Except for the Fabaceae species, nitrate leaching was reduced in deep, natural soils. The highest transpiration rates were associated with natural soils. All functions were modulated by plant families or species. Plant effects differed according to the observed function and the type and depth of the substrate. Fabaceae species grown on natural soils had the most noticeable patterns, allowing high biomass production and high water retention but also high nitrate leaching from deep pots. No single combination of factors enhanced simultaneously all studied ecosystem functions, highlighting that soil-plant interactions induce trade-offs between ecosystem functions. Substrate type and depth interactions are major drivers for green roof multifunctionality.

Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System

Directory of Open Access Journals (Sweden)

Therese Featherston

2016-09-01

Full Text Available Aim We have recently identified and characterized cancer stem cell (CSC subpopulations within moderately differentiated buccal mucosal squamous cell carcinoma (MDBMSCC. We hypothesized that these CSCs express components of the renin-angiotensin system (RAS.Methods 3,3-Diaminobenzidine (DAB immunohistochemical (IHC staining was performed on formalin-fixed paraffin-embedded MDBMSCC samples to investigate the expression of the components of the RAS: pro(renin receptor (PRR, angiotensin converting enzyme (ACE, angiotensin II receptor 1 (ATIIR1 and angiotensin II receptor 2 (ATIIR2. NanoString mRNA gene expression analysis and Western Blotting (WB were performed on snap-frozen MDBMSCC samples to confirm gene expression and translation of these transcripts, respectively. Double immunofluorescent (IF IHC staining of these components of the RAS with the embryonic stem cell markers OCT4 or SALL4 was performed to demonstrate their localization in relation to the CSC subpopulations within MDBMSCC.Results DAB IHC staining demonstrated expression of PRR, ACE, ATIIR1 and ATIIR2 in MDBMSCC. IF IHC staining showed that PRR was expressed by the CSC subpopulations within the tumor nests, the peri-tumoral stroma and the endothelium of the microvessels within the peri-tumoral stroma. ATIIR1 and ATIIR2 were localized to the CSC subpopulations within the tumor nests and the peri-tumoral stroma, while ACE was localized to the endothelium of the microvessels within the peri-tumoral stroma. WB and NanoString analyses confirmed protein expression and transcription activation of PRR, ACE and ATIIR1 but not of ATIIR2, respectively.

Strain rate effects on localized necking in substrate-supported metal layers

OpenAIRE

BEN BETTAIEB, Mohamed; ABED-MERAIM, Farid

2017-01-01

Due to their good mechanical and technological performances, thin substrate-supported metal layers are increasingly used as functional components in flexible electronic devices. Consequently, the prediction of necking, and the associated limit strains, for such components is of major academic and industrial importance. The current contribution aims to numerically investigate the respective and combined effects of strain rate sensitivity of the metal layer and the addition of an elastomer l...

Direct-current substrate bias effects on amorphous silicon sputter-deposited films for thin film transistor fabrication

International Nuclear Information System (INIS)

Jun, Seung-Ik; Rack, Philip D.; McKnight, Timothy E.; Melechko, Anatoli V.; Simpson, Michael L.

2005-01-01

The effect that direct current (dc) substrate bias has on radio frequency-sputter-deposited amorphous silicon (a-Si) films has been investigated. The substrate bias produces a denser a-Si film with fewer defects compared to unbiased films. The reduced number of defects results in a higher resistivity because defect-mediated conduction paths are reduced. Thin film transistors (TFTs) that were completely sputter deposited were fabricated and characterized. The TFT with the biased a-Si film showed lower leakage (off-state) current, higher on/off current ratio, and higher transconductance (field effect mobility) than the TFT with the unbiased a-Si film

An Al₂O₃ Gating Substrate for the Greater Performance of Field Effect Transistors Based on Two-Dimensional Materials.

Science.gov (United States)

Yang, Hang; Qin, Shiqiao; Zheng, Xiaoming; Wang, Guang; Tan, Yuan; Peng, Gang; Zhang, Xueao

2017-09-22

We fabricated 70 nm Al₂O₃ gated field effect transistors based on two-dimensional (2D) materials and characterized their optical and electrical properties. Studies show that the optical contrast of monolayer graphene on an Al₂O₃/Si substrate is superior to that on a traditional 300 nm SiO₂/Si substrate (2.4 times). Significantly, the transconductance of monolayer graphene transistors on the Al₂O₃/Si substrate shows an approximately 10-fold increase, due to a smaller dielectric thickness and a higher dielectric constant. Furthermore, this substrate is also suitable for other 2D materials, such as WS₂, and can enhance the transconductance remarkably by 61.3 times. These results demonstrate a new and ideal substrate for the fabrication of 2D materials-based electronic logic devices.

Phonon scattering in graphene over substrate steps

International Nuclear Information System (INIS)

Sevinçli, H.; Brandbyge, M.

2014-01-01

We calculate the effect on phonon transport of substrate-induced bends in graphene. We consider bending induced by an abrupt kink in the substrate, and provide results for different step-heights and substrate interaction strengths. We find that individual substrate steps reduce thermal conductance in the range between 5% and 47%. We also consider the transmission across linear kinks formed by adsorption of atomic hydrogen at the bends and find that individual kinks suppress thermal conduction substantially, especially at high temperatures. Our analysis show that substrate irregularities can be detrimental for thermal conduction even for small step heights.

Substrate modulation of fatty acid effects on energization and respiration of kidney proximal tubules during hypoxia/reoxygenation.

Directory of Open Access Journals (Sweden)

Anja Bienholz

Full Text Available Kidney proximal tubules subjected to hypoxia/reoxygenation develop a nonesterified fatty acid-induced energetic deficit characterized by persistent partial mitochondrial deenergization that can be prevented and reversed by citric acid cycle substrates. To further assess the role of competition between fatty acids and substrates on inner membrane substrate carriers in the deenergization and the contribution to deenergization of fatty acid effects on respiratory function, digitonin-permeabilized rabbit and mouse tubules were studied using either addition of exogenous oleate after control normoxic incubation or increases of endogenous fatty acids produced by hypoxia/reoxygenation. The results demonstrated major effects of matrix oxaloacetate accumulation on succinate-supported energization and respiration and their modification by fatty acids. Improvements of energization in the presence of fatty acids by glutamate were shown to result predominantly from lowering matrix oxaloacetate rather than from amelioration of transmembrane cycling of fatty acids and uncoupling. Mouse tubules had 2.5 fold higher rates of succinate utilization, which resulted in stronger effects of oxaloacetate accumulation than rabbit tubules. Hypoxia/reoxygenation induced respiratory inhibition that was more severe for complex I-dependent substrates. Fatty acids themselves did not acutely contribute to this respiratory inhibition, but lowering them during 60 min. reoxygenation to allow recovery of ATP during that period alleviated it. These data clarify the basis for the nonesterified fatty acid-induced mitochondrial energetic deficit in kidney proximal tubules that impairs structural and functional recovery and provide insight into interactions that need to be considered in the design of substrate-based interventions to improve mitochondrial function.

Acute and chronic role of nitric oxide, renin-angiotensin system and sympathetic nervous system in the modulation of calcium sensitization in Wistar Rats

Czech Academy of Sciences Publication Activity Database

Brunová, Aneta; Bencze, Michal; Behuliak, Michal; Zicha, Josef

2015-01-01

Roč. 64, č. 4 (2015), s. 447-457 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP304/12/0259; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : blood pressure * kalcium sensitization * Rho kinase * nitric oxide * renin-angiotensin system * sympathetic nervous system * fasudil Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.643, year: 2015

Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes

DEFF Research Database (Denmark)

Persson, Frederik; Lindhardt, Morten; Rossing, Peter

2016-01-01

Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can...... prevent development of microalbuminuria. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials, with a population of patients with type 2 diabetes and normoalbuminuria, comparing angiotensin-converting enzyme inhibitors (ACEis......-cause mortality(p=0.07). Conclusions: We conclude that in patients with type 2 diabetes and normoalbuminuria, early intervention with ACEis or ARBs reduces the risk for development of microalbuminuria....

The effects of diurnal Ramadan fasting on energy expenditure and substrate oxidation in healthy men.

Science.gov (United States)

Alsubheen, Sana'a A; Ismail, Mohammad; Baker, Alicia; Blair, Jason; Adebayo, Adeboye; Kelly, Liam; Chandurkar, Vikram; Cheema, Sukhinder; Joanisse, Denis R; Basset, Fabien A

2017-12-01

The study aimed to examine the effects of diurnal Ramadan fasting (RF) on substrate oxidation, energy production, blood lipids and glucose as well as body composition. Nine healthy Muslim men (fasting (FAST) group) and eight healthy non-practicing men (control (CNT) group) were assessed pre- and post-RF. FAST were additionally assessed at days 10, 20 and 30 of RF in the morning and evening. Body composition was determined by hydrodensitometry, substrate oxidation and energy production by indirect calorimetry, blood metabolic profile by biochemical analyses and energy balance by activity tracker recordings and food log analyses. A significant group×time interaction revealed that chronic RF reduced body mass and adiposity in FAST, without changing lean mass, whereas CNT subjects remained unchanged. In parallel to these findings, a significant main diurnal effect (morning v. evening) of RF on substrate oxidation (a shift towards lipid oxidation) and blood metabolic profile (a decrease in glucose and an increase in total cholesterol and TAG levels, respectively) was observed, which did not vary over the course of the Ramadan. In conclusion, although RF induces diurnal metabolic adjustments (morning v. evening), no carryover effect was observed throughout RF despite the extended daily fasting period (18·0 (sd 0·3) h) and changes in body composition.

Power electronics substrate for direct substrate cooling

Science.gov (United States)

Le, Khiet [Mission Viejo, CA; Ward, Terence G [Redondo Beach, CA; Mann, Brooks S [Redondo Beach, CA; Yankoski, Edward P [Corona, CA; Smith, Gregory S [Woodland Hills, CA

2012-05-01

Systems and apparatus are provided for power electronics substrates adapted for direct substrate cooling. A power electronics substrate comprises a first surface configured to have electrical circuitry disposed thereon, a second surface, and a plurality of physical features on the second surface. The physical features are configured to promote a turbulent boundary layer in a coolant impinged upon the second surface.

GaN-Ready Aluminum Nitride Substrates for Cost-Effective, Very Low Dislocation Density III-Nitride LEDs

International Nuclear Information System (INIS)

Schujman, Sandra; Schowalter, Leo

2011-01-01

The objective of this project was to develop and then demonstrate the efficacy of a cost effective approach for a low defect density substrate on which AlInGaN LEDs can be fabricated. The efficacy of this 'GaN-ready' substrate would then be tested by growing high efficiency, long lifetime InxGa1-xN blue LEDs. The approach used to meet the project objectives was to start with low dislocation density AlN single-crystal substrates and grow graded Al x Ga 1-x N layers on top. Pseudomorphic Al x Ga 1-x N epitaxial layers grown on bulk AlN substrates were used to fabricate light emitting diodes and demonstrate better device performance as a result of the low defect density in these layers when benched marked against state-of-the-art LEDs fabricated on sapphire substrates. The pseudomorphic LEDs showed excellent output powers compared to similar wavelength devices grown on sapphire substrates, with lifetimes exceeding 10,000 hours (which was the longest time that could reliably be estimated). In addition, high internal quantum efficiencies were demonstrated at high driving current densities even though the external quantum efficiencies were low due to poor photon extraction. Unfortunately, these pseudomorphic LEDs require high Al content so they emit in the ultraviolet. Sapphire based LEDs typically have threading dislocation densities (TDD) > 10 8 cm -2 while the pseudomorphic LEDs have TDD (le) 10 5 cm -2 . The resulting TDD, when grading the Al x Ga 1-x N layer all the way to pure GaN to produce a 'GaN-ready' substrate, has varied between the mid 10 8 down to the 10 6 cm -2 . These inconsistencies are not well understood. Finally, an approach to improve the LED structures on AlN substrates for light extraction efficiency was developed by thinning and roughening the substrate.

Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

Science.gov (United States)

Bokma, Jouke P; Winter, Michiel M; van Dijk, Arie P; Vliegen, Hubert W; van Melle, Joost P; Meijboom, Folkert J; Post, Martijn C; Berbee, Jacqueline K; Boekholdt, S Matthijs; Groenink, Maarten; Zwinderman, Aeilko H; Mulder, Barbara J M; Bouma, Berto J

2018-04-03

The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] 0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EFtetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905. © 2017 American Heart Association, Inc.

Effects of substrate pretreatments on diamond synthesis for Si{sub 3}N{sub 4} based ceramics

Energy Technology Data Exchange (ETDEWEB)

Shibuya, Y. [Prefectural Industrial Research Inst., Shizuoka (Japan); Takaya, M. [Chiba Institute of Technology, Tsudanuma 2-chome, Narashino-shi, 275 (Japan)

1998-07-08

Diamond synthesis for Si{sub 3}N{sub 4} ceramics after various substrate pretreatments has been carried out by the microwave-plasma enhanced chemical vapor deposition (CVD) method using a mixture of methane and hydrogen gases. Four types of pretreatments for various substrates were performed as follows: scratching with diamond powder (I), applying O{sub 2}-C{sub 2}H{sub 2} combustion flames (II), polishing with alumina (III), and platinum vapor deposition (IV). The products deposited on the substrate were examined with micro-Raman spectroscopy, scanning electron microscopy (SEM) and an X-ray diffractometer (XRD). It was found that the application of O{sub 2}-C{sub 2}H{sub 2} flames as a pretreatment of the substrate in diamond synthesis was suitable, because a higher density of diamond nucleation could be obtained, and a film-like diamond could be formed on the surface in a shorter time than without applying them. The diamond could be synthesized on the surface for all four types of substrate pretreatments performed in the present study. The effects of the substrate pretreatments on the surface morphology of grown diamond were that a film-like diamond for (I) or (II), a particle-like diamond for (III) and a particle and/or a film-like diamond for (IV) were formed on the surface. The surface morphology of grown diamond depended very much on the substrate temperature under deposition. (orig.) 18 refs.

Substrate-bias effect on the breakdown characteristic in a new silicon high-voltage device structure

International Nuclear Information System (INIS)

Li Qi; Wang Weidong; Zhao Qiuming; Wei Xueming

2012-01-01

A novel silicon double-RESURF LDMOS structure with an improved breakdown characteristic by substrate bias technology (SB) is reported. The P-type epitaxial layer is embedded between an N-type drift region and an N-type substrate to block the conduction path in the off-state and change the distributions of the bulk electric field. The substrate bias strengthens the charge share effect of the drift region near the source, and the vertical electric field peak under the drain is decreased, which is especially helpful in improving the vertical breakdown voltage in a lateral power device with a thin drift region. The numerical results by MEDICI indicate that the breakdown voltage of the proposed device is increased by 97% compared with a conventional LDMOS, while maintaining a lowon-resistance. (semiconductor devices)