B-Type Natriuretic Peptide and Prognosis in Heart Failure Patients With Preserved and Reduced Ejection Fraction

NARCIS (Netherlands)

van Veldhuisen, Dirk J.; Linssen, Gerard C. M.; Jaarsma, Tiny; van Gilst, Wiek H.; Hoes, Arno W.; Tijssen, Jan G. P.; Paulus, Walter J.; Voors, Adriaan A.; Hillege, Hans L.

2013-01-01

Objectives This study sought to determine the prognostic value of B-type natriuretic peptide (BNP) in patients with heart failure with preserved ejection fraction (HFPEF), in comparison to data in HF patients with reduced left ventricular (LV) EF ( Background Management of patients with HFPEF is

The human endolymphatic sac expresses natriuretic peptides

DEFF Research Database (Denmark)

Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

2017-01-01

: Several natriuretic peptides were found expressed significantly in the ES, including uroguanylin and brain natriuretic peptide, but also peptides regulating vascular tone, including adrenomedullin 2. In addition, both neurophysin and oxytocin (OXT) were found significantly expressed. All peptides were...... verified by immunohistochemistry. CONCLUSION: The present data support the hypothesis that the human ES may have an endocrine/paracrine capacity through expression of several peptides with potent natriuretic activity. Furthermore, the ES may influence the hypothalamo-pituitary-adrenal axis and may regulate...... vasopressin receptors and aquaporin-2 channels in the inner ear via OXT expression. We hypothesize that the ES is likely to regulate inner ear endolymphatic homeostasis, possibly through secretion of several peptides, but it may also influence systemic and/or intracranial blood pressure through direct...

Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-ß mediated fibrosis

LENUS (Irish Health Repository)

Watson, Chris J

2012-07-07

AbstractBackgroundMechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts’ response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.Methods and resultsThe effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.ConclusionWe postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.

Impact of epitope specificity and precursor maturation in pro-B-type natriuretic peptide measurement

DEFF Research Database (Denmark)

Goetze, J.P.; Dahlstrom, U.; Alehagen, U.

2008-01-01

with different epitope specificities in a cohort of elderly patients presenting with symptoms associated with heart failure (n = 415). RESULTS: Comparison of N-terminal proBNP with proBNP 1-76 measurement in plasma revealed a high correlation on regression analysis (r(2) = 0.91, P ..., the proBNP 1-76 assay measured lower concentrations in the high range than the N-terminal proBNP assay. Correlations between assay measurements in a clinical setting were comparable for all the assays (r(2) approximately 0.57-0.83), and ROC analyses revealed area-under-the-curve values ranging between 0......BACKGROUND: Cardiac-derived natriuretic peptides are sensitive plasma markers of cardiac dysfunction. Recent reports have disclosed a more complex molecular heterogeneity of B-type natriuretic peptide precursor (proBNP)-derived peptides than previously suggested. In this study, we examined...

Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease.

Science.gov (United States)

Neuhold, Stephanie; Huelsmann, Martin; Strunk, Guido; Stoiser, Brigitte; Struck, Joachim; Morgenthaler, Nils G; Bergmann, Andreas; Moertl, Deddo; Berger, Rudolf; Pacher, Richard

2008-07-22

This study sought to evaluate the predictive value of copeptin over the entire spectrum of heart failure (HF) and compare it to the current benchmark markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Vasopressin has been shown to increase with the severity of chronic HF. Copeptin is a fragment of pre-pro-vasopressin that is synthesized and secreted in equimolar amounts to vasopressin. Both hormones have a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin, copeptin is very stable in vitro. The predictive value of copeptin has been shown in advanced HF, where it was superior to BNP for predicting 24-month mortality. This was a long-term observational study in 786 HF patients from the whole spectrum of heart failure (New York Heart Association [NYHA] functional class I to IV, BNP 688 +/- 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular ejection fraction 25 +/- 10% [range 5% to 65%]). The NYHA functional class was the most potent single predictor of 24-month outcome in a stepwise Cox regression model. The BNP, copeptin, and glomerular filtration rate were related to NYHA functional class (p linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this study, but the markers seem to be closely related.

The Preoperative Level of B-Type Natriuretic Peptides and the Results of Clinical and Functional Studies of Cardiosurgical Patients

Directory of Open Access Journals (Sweden)

I. A. Kozlov

2009-01-01

Full Text Available Objective: to study the plasma content of B-type natriuretic peptides in coronary heart disease patients prepared for surgery under extracorporeal circulation and to assess the association of the level of these biomarkers with the data of clinical and functional studies. Material and methods. The levels of active B-type natriuretic peptide were determined by immunofluoresence assay in the blood of 52 patients aged 57.8±1 years. The patients’ baseline clinical condition was in New York Heart Association (NYHA Functional Class I—IV. The left ventricular ejection fraction was 59.6±1.2%. The plasma concentration of the inactive N-terminal fragment of the BNP prohormone (NT-proBNP was estimated by electric chemiluminescence technique in 61 patients aged 54.6±1.18 years. The patients’ clinical condition was in NYHA Functional Class II—IV. The left ventricular ejection fraction was 51.5±1.6%. Results. The plasma content of B-type natriuretic peptide in the examinees was 48.5±5.9 pg/ml. The level of the biomarker correlated with the NYHA functional class (r=0.4; p=0.005, the electrocardiographic signs of postinfarct cardiosclerosis (r=0.29; p=0.04, and left ventricular ejection fraction (r=-0.41; p=0.003, and end-systolic volume (r=0.32; p=0.03. The plasma concentration of inactive NT-proBNP was 659.4±91.6 pg/ml. The level of the biomarker correlated with the NYHA functional class (r=0.4; p=0.002, the stage of circulatory insufficiency as described by I. D. Strazhesko and V. Kh. Vasilenko (r=0.49; p=0.001, and left ventricular ejection fraction (r=-0.45; p=0.001, and end-diastolic (r=0.39; p=0.002 and end-systolic (r=0.42; p=0.001 volumes. In patients with the values of the biomarker of less than 1000 pg/ml, the latter was related to age (r=0.3; p=0.047. Conclusion. The study of the level of B-type natriuretic peptides in cardiosurgical patients with coronary heart disease, prepared for surgery under extracorporeal circulation, suggests

Endothelial actions of atrial and B-type natriuretic peptides.

Science.gov (United States)

Kuhn, Michaela

2012-05-01

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics.

Science.gov (United States)

Torres-Courchoud, I; Chen, H H

2016-10-01

Natriuretic peptides are a family of peptides with similar structures, but are genetically distinct with diverse actions in cardiovascular, renal and fluid homeostasis. The family consists of an atrial natriuretic peptide (ANP) and a brain natriuretic peptide (BNP) of myocardial cell origin, a C-type natriuretic peptide (CNP) of endothelial origin, and a urodilatin (Uro) which is processed from a prohormone ANP in the kidney. Nesiritide, a human recombinant BNP, was approved by the Federal Drug Administration (FDA) for the management of acute heart failure (AHF) in 2001. Human recombinant ANP (Carperitide) was approved for the same clinical indication in Japan in 1995, and human recombinant Urodilatin (Ularitide) is currently undergoing phase III clinical trial (TRUE AHF). This review will provide an update on important issues regarding the role of BNP in fluid hemostasis as a biomarker and therapeutics in AHF. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

B-Type Natriuretic Peptide Reactivity to Mental Stress and Exercise: Role of Obesity and Hemodynamics

Science.gov (United States)

2009-08-25

Clinically, BNP is important in diagnosis/ differential diagnosis in individuals with suspected HF, with a decision cut-point of 100 pg/ml now accepted as...the context of obesity-related disparity in BNP levels or action. Based on the differential hemodynamic reactivity patterns associated with...Arch Intern Med. 2004, 164:2247- 2252. 124 141. Mehra MR, Uber PA, Park MH, et al.: Obesity and suppressed B-type natriuretic peptide levels in

Clinical implications of B-type natriuretic peptide and N-terminal pro--B-type natriuretic peptide in the care of the vascular surgery patient.

Science.gov (United States)

Wayne Causey, Marlin; Singh, Niten

2014-12-01

B-type natriuretic peptide (also known as brain natriuretic peptide or BNP) is a physiologic marker that is often used to assess a patient's global cardiovascular health. BNP is secreted from the ventricular cardiac myocytes in response to stretch that occurs due to increased intravascular volume. PreproBNP is cleaved into BNP and N-terminal proBNP (NT proBNP) to cause diuresis, natriuresis, and vasodilation, and can be measured with a blood laboratory assay test or point-of-care testing. BNP/NT proBNP has been most extensively studied in the diagnosis and management of heart failure, but within the past 5 years, interest has carried over to vascular surgery patients. Studies have demonstrated that elevated levels of BNP/NT-proBNP (typically >100 pg/mL/>300 pg/mL) are associated with major adverse cardiac events at 30 and 180 days. Additional analysis of BNP/NT-proBNP has demonstrated that patients can be classified as very low risk (400 pg/mL). BNP/NT-proBNP in the low- and very-low-risk groups suggests patients are unlikely to have a major adverse cardiac event. An elevated BNP/NT-proBNP, excluding those with reasons for abnormal values, suggests the need for additional risk stratification and medical risk factor optimization. A preoperative measure of BNP or NT-proBNP affords an easy and rapid opportunity to individually and objectively quantify perioperative cardiovascular risk. Recent studies have also identified other biomarkers, none superior to BNP or NT-proBNP, but that, when used concomitantly, aid in further stratifying perioperative risk and will likely be the focus of future investigations. Published by Elsevier Inc.

Comparative evaluation of B-type natriuretic peptide and mid-regional pro-A-type natriuretic peptide changes from admission to discharge in prognosis of acute decompensated heart failure patients.

Science.gov (United States)

Stenner, Elisabetta; Buiatti, Alessandra; Barbati, Giulia; Merlo, Marco; Sinagra, Gianfranco; Biasioli, Bruno

2012-01-01

Mid-regional pro-A-type natriuretic peptide (MRproANP) seems to be non-inferior compared to B-type natriuretic peptide (BNP) for heart failure diagnosis and prognosis; however, no previous studies have investigated the MRproANP in-hospital changes in prognostic role. This study aimed to compare the prognostic accuracy of BNP and MRproANP in-hospital changes in acute decompensated heart failure (ADHF) patients. 37 patients with either admission/pre-discharge BNP and MRproANP data, were investigated. The combined endpoint was cardiovascular death/heart transplantation/readmission for HF. BNP and MRproANP had a median decrease of 55% [72;45] and 21% [40; 11] respectively in event-free patients; BNP decrease of 34% [48; 29] but MRproANP increase of 4% [-7; 25] in patients with cardiovascular events. Prognostic accuracy of deltaBNP and deltaMRproANP was similar. MRproANP basically trends up in patients with worse outcome and decreases in event-free patients, likely leading to a simpler interpretation although the prognostic accuracy is similar for both peptides.

Discriminating between cardiac and pulmonary dysfunction in the general population with dyspnea by plasma pro-B-type natriuretic peptide

DEFF Research Database (Denmark)

Mogelvang, R; Goetze, JP; Schnohr, P

2007-01-01

OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac...... the expected concentration of plasma proBNP based on age and gender was established for dyspneic subjects: an actual plasma proBNP concentration below half of the expected value ruled out left ventricular systolic and diastolic dysfunction (sensitivity 100%, 95% CI 100% to 100%; specificity 15%, 95% CI 12...

Cardiac effects of 3 months treatment of acromegaly evaluated by magnetic resonance imaging and B-type natriuretic peptides

DEFF Research Database (Denmark)

Andreassen, Mikkel; Faber, Jens; Kjær, Andreas

2010-01-01

Long-term treatment of acromegaly prevents aggravation and reverses associated heart disease. A previous study has shown a temporary increase in serum levels of the N-terminal fraction of pro B-type natriuretic peptide (NT-proBNP) suggesting an initial decline in cardiac function when treatment...... of acromegaly is initiated. This was a three months prospective study investigating short-term cardiac effects of treatment in acromegalic patients. Cardiac function was evaluated by the gold standard method cardiac magnetic resonance imaging (CMRI) and circulating levels of B-type natriuretic peptides (BNP......) (95% CI 3-14), P = 0.007) and an increase in levels of BNP (median (ranges) 7 (0.58-286) vs. 20 (1-489) pg/mL, P = 0.033) and of NT-proBNP (63 (20-1004) vs. 80 (20-3391) pg/mL, P = 0.027). Assessed by the highly sensitive and precise CMRI method, 3 months treatment of acromegaly resulted...

Relation of N-Terminal Pro B-Type Natriuretic Peptide Levels After Symptom-Limited Exercise to Baseline and Ischemia Levels

NARCIS (Netherlands)

van der Zee, P. Marc; Verberne, Hein J.; van Spijker, Rianne C.; van Straalen, Jan P.; Fischer, Johan C.; Sturk, Augueste; van Eck-Smit, Berthe L. F.; de Winter, Robbert J.

2009-01-01

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion

Management of Chronic Heart Failure Guided by Individual N-Terminal Pro-B-Type Natriuretic Peptide Targets Results of the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) Study

NARCIS (Netherlands)

Eurlings, Luc W. M.; van Pol, Petra E. J.; Kok, Wouter E.; van Wijk, Sandra; Lodewijks-van der Bolt, Cara; Balk, Aggie H. M. M.; Lok, Dirk J. A.; Crijns, Harry J. G. M.; van Kraaij, Dave J. W.; de Jonge, Nicolaas; Meeder, Joan G.; Prins, Martin; Pinto, Yigal M.

2010-01-01

Objectives The purpose of this study was to assess whether management of heart failure (HF) guided by an individualized N-terminal pro-B-type natriuretic peptide (NT-proBNP) target would lead to improved outcome compared with HF management guided by clinical assessment alone. Background Natriuretic

Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care

DEFF Research Database (Denmark)

Hildebrandt, Per; Collinson, Paul O; Doughty, Robert N

2010-01-01

The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards.......The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards....

Associations between N-terminal pro-B-type natriuretic peptide and cardiac function in adults with corrected tetralogy of Fallot

NARCIS (Netherlands)

J.A. Eindhoven (Jannet); M.E. Menting (Myrthe); A.E. van den Bosch (Annemien); J.A.A.E. Cuypers (Judith); T.P.E. Ruys (Titia); M. Witsenburg (Maarten); J.S. Vletter-McGhie (Jackie); H. Boersma (Eric); J.W. Roos-Hesselink (Jolien)

2014-01-01

textabstractBackground Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with

N-terminal-pro-B-type natriuretic peptide during pharmacological heart rate reduction in hyperthyroidism

DEFF Research Database (Denmark)

Schultz, M; Kistorp, C; Corell, P

2009-01-01

days. Before treatment, N-terminal-pro-B-type natriuretic peptide was independently associated with thyroid function (free triiodothyronine-index, r=0.64, p=0.001) and the hemoglobin concentration (r=-0.36, p=0.031). The verapamil treatment induced a decrease in parameters reflecting cardiac function......-index decreased from median 319 to 315 arbitrary units (p=0.039) and free triiodothyronine-index increased from 8.6 to 9.9 arbitrary units (p=0.010). No changes in echocardiographic parameters were observed. A decrease in resting heart rate in untreated hyperthyroidism due to verapamil treatment did not result...

N-Terminal Pro-B-Type Natriuretic Peptide and Phonocardiography in Differentiating Innocent Cardiac Murmurs from Congenital Cardiac Anomalies in Asymptomatic Puppies

NARCIS (Netherlands)

Marinus, S M; Engelen, H.G.H.; Szatmári, V.

2017-01-01

Background: Differentiating innocent cardiac murmurs from murmurs caused by congenital cardiac anomalies can be challenging with auscultation alone in asymptomatic puppies. Hypothesis: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and phonocardiograms recorded by an

Comparability of Results between Point-of-Care and Automated Instruments to Measure B-type Natriuretic Peptide

OpenAIRE

Shah, Kevin; Terracciano, Garrett J.; Jiang, Kevin; Maisel, Alan S.; Fitzgerald, Robert L.

2010-01-01

Objectives: Heart failure is one of the leading causes of death in the U.S. The incorporation of B-type natriuretic peptide (BNP) measurements when triaging patients presenting with shortness of breath has improved the diagnostic and prognostic ability of physicians. Currently, there are no point-of-care systems for quantifying BNP that can be used without sacrificing accuracy. We compared the analytical performance of the Abbott i-STAT analyzer, a handheld point-of-care system for measuring ...

Practical use of natriuretic peptide measurement

DEFF Research Database (Denmark)

Husby, Simon; Lind, Bent; Goetze, Jens P

2012-01-01

To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) measurement among doctors using this biomarker.......To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) measurement among doctors using this biomarker....

Preoperative B-type natriuretic peptides in patients undergoing ...

African Journals Online (AJOL)

Background: A plethora of studies have shown elevated preoperative natriuretic peptide measurements to predict ... In October 2014, we searched the following online databases, ... excluded because they had been retracted due to fraud.

Role of B-Type Natriuretic Peptide and N-Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus.

Science.gov (United States)

Wolsk, Emil; Claggett, Brian; Pfeffer, Marc A; Diaz, Rafael; Dickstein, Kenneth; Gerstein, Hertzel C; Lawson, Francesca C; Lewis, Eldrin F; Maggioni, Aldo P; McMurray, John J V; Probstfield, Jeffrey L; Riddle, Matthew C; Solomon, Scott D; Tardif, Jean-Claude; Køber, Lars

2017-05-29

Natriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B-type natriuretic peptide (BNP) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus. Patients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow-up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/NT-proBNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT-proBNP to best risk models. Overall, BNP and NT-proBNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77-0.82, P type 2 diabetes mellitus, BNP and NT-proBNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01147250. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Clinically relevant diagnostic research in primary care : the example of B-type natriuretic peptides in the detection of heart failure

NARCIS (Netherlands)

Kelder, Johannes C.; Rutten, Frans H.; Hoes, Arno W.

With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart

The relationship between C-type natriuretic peptide and cognitive impairment in older patients with Type 2 diabetes

International Nuclear Information System (INIS)

Li Xinling; Zhu Xiangyang; Huang Huaiyu; Jin Yan

2011-01-01

Objective: To investigate the relationship between C-type natriuretic peptide and cognitive impairment in older patients with type 2 diabetes, and to explore the pathogenesis of diabetic cognitive impairment. Methods: According to the Montreal Cognitive Assessment (MoCA) scores, 80 type 2 diabetic patients over the age of 60 years were divided into two groups, one group including 31 cases with cognitive impairment, the other 49 patients with non-cognitive impairment. And 80 normal participants were selected as the control group. Plasma level of C-type natriuretic peptide was measured by radio-immunity assay in all subjects. The changes and associations of the plasma C-type natriuretic peptide level among three groups was analyzed. Result: In the non-cognitive impairment group, plasma level of C-type natriuretic peptide was higher than that in the control group (P<0.01). But the plasma level of C-type natriuretic peptide in the cognitive impairment group was degraded, significantly deferent with those in the control group and the non-cognitive impairment group (P<0.01). MoCA scores of the cognitive impairment group positively correlated with plasma level of C-type natriuretic peptide (r=0.513, P<0.01). Conclusion: In the early period of type 2 diabetes,the secretion of C-type natriuretic peptide was increased. When diabetic cognitive impairment complicated,the secretion of C-type natriuretic peptide was decompensated. Then plasma level of C-type natriuretic peptide become low. The level of C-type natriuretic peptide closely correlated with diabetic cognitive impairment. It was suggested that diabetic angiopathies may act an important role in the pathogenesis of diabetic cognitive impairment. (authors)

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 4: Prognostic value of B-type natriuretic peptides (BNP and NT-proBNP) in community-acquired pneumonia.

Science.gov (United States)

Hodgson, David; Nee, Patrick; Sultan, Laith

2012-10-01

A short cut review was carried out to establish the prognostic value of B-type natriuretic peptides (BNP and NT-proBNP) in community acquired pneumonia (CAP). Three cohort studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line was that B-type natriuretic peptides have prognostic value in CAP but further prospective studies were needed to assess their application in clinical practice.

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease

DEFF Research Database (Denmark)

Mouridsen, Mette R; Sajadieh, Ahmad; Carlsen, Christian M

2015-01-01

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATE...... = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP....

Prospective Associations of B-Type Natriuretic Peptide With Markers of Left Ventricular Function in Individuals With and Without Type 2 Diabetes An 8-year follow-up of the Hoorn Study

NARCIS (Netherlands)

Kroon, M.H.; Diamant, M.; van den Hurk, K.; Boomsma, F.; Alssema, M.J.; Nijpels, G.; Kamp, O.; Paulus, W.J.; Stehouwer, C.D.A.; Dekker, J.M.; Henry, R.M.

2012-01-01

OBJECTIVE - Heart failure is common in individuals with type 2 diabetes, and early detection of individuals at risk may offer opportunities for prevention. We aimed to explore 1) prospective associations of B-type natriuretic peptide (BNP) levels in a non-heart failure range with changes in markers

Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance.

Science.gov (United States)

Kanai, Yugo; Yasoda, Akihiro; Mori, Keita P; Watanabe-Takano, Haruko; Nagai-Okatani, Chiaki; Yamashita, Yui; Hirota, Keisho; Ueda, Yohei; Yamauchi, Ichiro; Kondo, Eri; Yamanaka, Shigeki; Sakane, Yoriko; Nakao, Kazumasa; Fujii, Toshihito; Yokoi, Hideki; Minamino, Naoto; Mukoyama, Masashi; Mochizuki, Naoki; Inagaki, Nobuya

2017-11-01

Although peptides are safe and useful as therapeutics, they are often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy for increasing the efficacy of peptide therapies. Natriuretic peptide receptor B (NPR-B) and its naturally occurring ligand, C-type natriuretic peptide (CNP), are potent stimulators of endochondral bone growth, and activating the CNP/NPR-B system is expected to be a powerful strategy for treating impaired skeletal growth. CNP is cleared by natriuretic peptide clearance receptor (NPR-C); therefore, we investigated the effect of reducing the rate of CNP clearance on skeletal growth by limiting the interaction between CNP and NPR-C. Specifically, we generated transgenic mice with increased circulating levels of osteocrin (OSTN) protein, a natural NPR-C ligand without natriuretic activity, and observed a dose-dependent skeletal overgrowth phenotype in these animals. Skeletal overgrowth in OSTN-transgenic mice was diminished in either CNP- or NPR-C-depleted backgrounds, confirming that CNP and NPR-C are indispensable for the bone growth-stimulating effect of OSTN. Interestingly, double-transgenic mice of CNP and OSTN had even higher levels of circulating CNP and additional increases in bone length, as compared with mice with elevated CNP alone. Together, these results support OSTN administration as an adjuvant agent for CNP therapy and provide a potential therapeutic approach for diseases with impaired skeletal growth.

Diurnal gene expression of lipolytic natriuretic peptide receptors in white adipose tissue

DEFF Research Database (Denmark)

Smith, Julie; Fahrenkrug, Jan; Jørgensen, Henrik L

2015-01-01

Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart, but the tem......Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart......, but the temporal expression profile of their cognate receptors has not been examined in white adipose tissue. We therefore collected peri-renal white adipose tissue and serum from WT mice. Tissue mRNA contents of NPRs - NPR-A and NPR-C, the clock genes Per1 and Bmal1, and transcripts involved in lipid metabolism...... in serum peaked in the active dark period (P=0.003). In conclusion, NPR-A and NPR-C gene expression is associated with the expression of clock genes in white adipose tissue. The reciprocal expression may thus contribute to regulate lipolysis and energy homeostasis in a diurnal manner....

Role of B-Type Natriuretic Peptide and N-Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

DEFF Research Database (Denmark)

Wolsk, Emil; Claggett, Brian; Pfeffer, Marc A

2017-01-01

-terminal prohormone B-type natriuretic peptide (NT-proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus. METHODS AND RESULTS: Patients with a recent acute coronary syndrome and type 2 diabetes mellitus were...... being in death (0.77-0.82, Pdiabetes...

Correlation of plasma B-type natriuretic peptide levels with metabolic risk markers.

Science.gov (United States)

Ahued-Ortega, José Armando; León-García, Plácido Enrique; Hernández-Pérez, Elizabeth

2018-04-17

Natriuretic peptide type B (BNP) is a marker of myocardium injury. This peptide has been associated with metabolic risk markers, although controversy exists in this regard. The aim of the present study was to determine the correlation of plasma BNP levels with metabolic risk parameters. A retrospective, observational study that included 152 patients, who were classified according to their clinical diagnosis as patients with metabolic syndrome. Plasma BNP levels and clinical metabolic parameters were assessed by using Spearmańs rank correlation coefficient. A significant inverse association with weight (r=-.408; p<.0001) and BMI (r=-.443; p<.001) was obtained. While a positive significant association with systolic pressure (r=.324; p<.001) was observed. A significant decrease was found in BNP levels and components of metabolic syndrome. (p<.05). Based on the results from this study, we can conclude that BNP determination could be an adequate metabolic marker. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children

NARCIS (Netherlands)

Boer, S.L. den; Rizopoulos, D.; Sarvaas, G.J.; Backx, A.P.; Harkel, A.D. Ten; Iperen, G.G. van; Rammeloo, L.A.; Tanke, R.B.; Boersma, E.; Helbing, W.A.; Dalinghaus, M.

2016-01-01

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated

Comparability of Results Between a Point-of-Care and an Automated Instrument for Measurement of B-Type Natriuretic Peptide

OpenAIRE

Shah, Kevin; Terracciano, Garrett J; Jiang, Kevin; Maisel, Alan S; Fitzgerald, Robert L

2010-01-01

Objectives: Heart failure is one of the leading causes of death in the U.S. The incorporation of B-type natriuretic peptide (BNP) measurements when triaging patients presenting with shortness of breath has improved the diagnostic and prognostic ability of physicians. Currently, there are no point-of-care systems for quantifying BNP that can be used without sacrificing accuracy. We compared the analytical performance of the Abbott i-STAT analyzer, a handheld point-of-care system for measuring ...

Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal pro B-type natriuretic peptide in the diagnosis of patients with atrial fibrillation and dyspnoea.

Science.gov (United States)

Eckstein, Jens; Potocki, Mihael; Murray, Karsten; Breidthardt, Tobias; Ziller, Ronny; Mosimann, Tamina; Klima, Theresia; Hoeller, Rebeca; Moehring, Berit; Sou, Seoung Mann; Rubini Gimenez, Maria; Morgenthaler, Nils G; Mueller, Christian

2012-10-01

Due to different release mechanisms, mid-regional pro-atrial natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for their diagnostic value in patients with AF and sinus rhythm (SR). Prospective cohort study. University hospital, emergency department. 632 consecutive patients presenting with acute dyspnoea. MR proANP and NT proBNP plasma levels were determined. The diagnosis of AHF was adjudicated by two independent cardiologists using all available data. Patients received long-term follow-up. AF was present in 151 patients (24%). MR proANP and NT proBNP levels were significantly higher in the AF group compared with the SR group (385 (258-598) versus 201 (89-375) pmol/l for MR proANP, pvalue for the diagnosis of AHF. The rhythm at presentation has to be taken into account because plasma levels of both peptides are significantly higher in patients with AF compared with SR.

Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor

International Nuclear Information System (INIS)

Johns, Douglas G.; Ao, Zhaohui; Heidrich, Bradley J.; Hunsberger, Gerald E.; Graham, Taylor; Payne, Lisa; Elshourbagy, Nabil; Lu, Quinn; Aiyar, Nambi; Douglas, Stephen A.

2007-01-01

Dendroaspis natriuretic peptide (DNP) is a newly-described natriuretic peptide which lowers blood pressure via vasodilation. The natriuretic peptide clearance receptor (NPR-C) removes natriuretic peptides from the circulation, but whether DNP interacts with human NPR-C directly is unknown. The purpose of this study was to test the hypothesis that DNP binds to NPR-C. ANP, BNP, CNP, and the NPR-C ligands AP-811 and cANP(4-23) displaced [ 125 I]-ANP from NPR-C with pM-to-nM K i values. DNP displaced [ 125 I]-ANP from NPR-C with nM potency, which represents the first direct demonstration of binding of DNP to human NPR-C. DNP showed high pM affinity for the GC-A receptor and no affinity for GC-B (K i > 1000 nM). DNP was nearly 10-fold more potent than ANP at stimulating cGMP production in GC-A expressing cells. Blockade of NPR-C might represent a novel therapeutic approach in augmenting the known beneficial actions of DNP in cardiovascular diseases such as hypertension and heart failure

Hyperinsulinemia correlates with low levels of plasma B-type natriuretic peptide in Japanese men irrespective of fat distribution

Directory of Open Access Journals (Sweden)

Nakatsuji Hideaki

2012-03-01

Full Text Available Abstract Background B-type natriuretic peptide (BNP, a member of the natriuretic peptide family, is a cardiac-derived secretory hormone with natriuretic, diuretic, and vasorelaxant activities. Intraabdominal fat accumulation is associated with atherosclerotic cardiovascular diseases and cardiac dysfunction. Circulating BNP levels are relatively low (within the normal limits in obesity and the metabolic syndrome. However, the relationship between plasma BNP levels and visceral fat accumulation in general population has not been reported. The present study analyzed the relationships between plasma BNP levels and various clinical variables, including insulin, visceral and subcutaneous fat area (VFA and SFA, respectively, in normal Japanese men. Methods The study (Victor-J study subjects were consecutive 500 Japanese male workers, who underwent a health checkup and were measured VFA and SFA by computed tomography. Results Age-adjusted simple linear regression analysis showed that log-BNP correlated positively with HDL-cholesterol, and negatively with VFA, log-immunoreactive insulin (IRI, log-triglyceride, and LDL-cholesterol, but not body mass index or SFA. Stepwise multiple regression analysis identified log-IRI and HDL-cholesterol as significant determinants of log-BNP. Subjects with IRI ≥5.5 μIU/mL had lower plasma BNP levels than those with IRI 2, visceral fat accumulation (VFA, cutoff value 100 cm2 and subcutaneous fat accumulation (SFA, cutoff value 128 cm2. Conclusions Our study showed that hyperinsulinemia correlated with low levels of plasma BNP in general men, irrespective of fat distribution. Trial registration UMIN 000004318.

C-type natriuretic peptide in prostate cancer

DEFF Research Database (Denmark)

Nielsen, Soeren Junge; Iversen, Peter; Rehfeld, Jens F.

2009-01-01

C-type natriuretic peptide (CNP) is expressed in the male reproductive organs in pigs. To examine whether the human prostate also expresses the CNP gene, we measured CNP and N-terminal proCNP in prostate cancer tissue extracts and performed immunohistochemical biopsy staining. Additionally, pro......CNP-derived peptides were quantitated in plasma from patients with prostate cancer. Blood was collected from healthy controls and patients before surgery for localized prostate cancer. Tissue extracts were prepared from tissue biopsies obtained from radical prostatectomy surgery. N-terminal proCNP, proCNP (1......-50) and CNP were measured in plasma and tissue extracts. Biopsies were stained for CNP-22 and N-terminal proCNP. Tissue extracts from human prostate cancer contained mostly N-terminal proCNP [median 5.3 pmol/g tissue (range 1.0-12.9)] and less CNP [0.14 pmol/g tissue (0.01-1.34)]. Immunohistochemistry...

Role of C-type natriuretic peptide in the function of normal human sperm

Directory of Open Access Journals (Sweden)

Hui Xia

2016-01-01

Full Text Available C-type natriuretic peptide (CNP is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B (NPR-B. Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods (such as immunolocalization, real time polymerase chain reaction and Western Blot, and then to evaluate the influence of CNP on sperm function i n vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.

Usefulness of Serum B-Type Natriuretic Peptide Levels in Comatose Patients Resuscitated from Out-of-Hospital Cardiac Arrest to Predict Outcome

DEFF Research Database (Denmark)

Frydland, Martin; Kjaergaard, Jesper; Erlinge, David

2016-01-01

N-terminal pro-B-type natriuretic (NT-proBNP) is expressed in the heart and brain, and serum levels are elevated in acute heart and brain diseases. We aimed to assess the possible association between serum levels and neurological outcome and death in comatose patients resuscitated from out......-of-hospital cardiac arrest (OHCA). Of the 939 comatose OHCA patients enrolled and randomized in the Targeted Temperature Management (TTM) trial to TTM at 33°C or 36°C for 24 hours, 700 were included in the biomarker substudy. Of these, 647 (92%) had serum levels of NT-proBNP measured 24, 48, and 72 hours after return...... of spontaneous circulation (ROSC). Neurological outcome was evaluated by the Cerebral Performance Category (CPC) score and modified Rankin Scale (mRS) at 6 months. Six hundred thirty-eight patients (99%) had serum NT-proBNP levels ≥125 pg/ml. Patients with TTM at 33°C had significantly lower NT-proBNP serum...

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide

NARCIS (Netherlands)

Klaassen, Sebastiaan H C; Tromp, Jasper; Nienhuis, Hans L A; van der Meer, Peter; van den Berg, Maarten P; Blokzijl, Hans; van Veldhuisen, Dirk J; Hazenberg, Bouke P C

2018-01-01

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center

Biosynthesis of cardiac natriuretic peptides

DEFF Research Database (Denmark)

Goetze, Jens Peter

2010-01-01

Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... peptides has only been elucidated during the last decade. The cellular synthesis including amino acid modifications and proteolytic cleavages has proven considerably more complex than initially perceived. Consequently, the elimination phase of the peptide products in circulation is not yet well....... An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

the natriuretic peptides: an expanding role in clinical medicine

African Journals Online (AJOL)

Enrique

body's defence against hypertension and plasma volume expansion.2 ... brain natriuretic peptide (B-type), secreted by the ventricle, and C-type peptide, ... Natriuretic peptides, on the other hand, are also stimulated in left ventricular dys- .... tions and in healthy controls as a com- .... stretching of the right ventricle causes.

C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice.

Science.gov (United States)

Kimura, Toru; Nojiri, Takashi; Hino, Jun; Hosoda, Hiroshi; Miura, Koichi; Shintani, Yasushi; Inoue, Masayoshi; Zenitani, Masahiro; Takabatake, Hiroyuki; Miyazato, Mikiya; Okumura, Meinoshin; Kangawa, Kenji

2016-02-19

Pulmonary fibrosis has high rates of mortality and morbidity; however, no effective pharmacological therapy has been established. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, selectively binds to the transmembrane guanylyl cyclase (GC)-B receptor and exerts anti-inflammatory and anti-fibrotic effects in various organs through vascular endothelial cells and fibroblasts that have a cell-surface GC-B receptor. Given the pathophysiological importance of fibroblast activation in pulmonary fibrosis, we hypothesized that the anti-fibrotic and anti-inflammatory effects of exogenous CNP against bleomycin (BLM)-induced pulmonary fibrosis were exerted in part by the effect of CNP on pulmonary fibroblasts. C57BL/6 mice were divided into two groups, CNP-treated (2.5 μg/kg/min) and vehicle, to evaluate BLM-induced (1 mg/kg) pulmonary fibrosis and inflammation. A periostin-CNP transgenic mouse model exhibiting CNP overexpression in fibroblasts was generated and examined for the anti-inflammatory and anti-fibrotic effects of CNP via fibroblasts in vivo. Additionally, we assessed CNP attenuation of TGF-β-induced differentiation into myofibroblasts by using immortalized human lung fibroblasts stably expressing GC-B receptors. Furthermore, to investigate whether CNP acts on human lung fibroblasts in a clinical setting, we obtained primary-cultured fibroblasts from surgically resected lungs of patients with lung cancer and analyzed levels of GC-B mRNA transcription. CNP reduced mRNA levels of the profibrotic cytokines interleukin (IL)-1β and IL-6, as well as collagen deposition and the fibrotic area in lungs of mice with bleomycin-induced pulmonary fibrosis. Furthermore, similar CNP effects were observed in transgenic mice exhibiting fibroblast-specific CNP overexpression. In cultured-lung fibroblasts, CNP treatment attenuated TGF-β-induced phosphorylation of Smad2 and increased mRNA and protein expression of α-smooth muscle actin and SM22�

Prognostic value of N-terminal pro-B-type natriuretic peptide in patients with acute coronary syndromes undergoing left main percutaneous coronary intervention

OpenAIRE

Jaberg, L; Toggweiler, S; Puck, M; Frank, M; Rufibach, K; Lüscher, T F; Corti, R

2011-01-01

BACKGROUND: Patients undergoing acute left main (LM) coronary artery revascularization have a high mortality and natriuretic peptides such as N-terminal pro-B-type (NT-proBNP) have been shown to have prognostic value in patients with acute coronary syndromes. The present study looked at the prognostic value of NT-proBNP in these patients. METHODS AND RESULTS: We studied all consecutive patients undergoing acute LM coronary artery percutaneous coronary intervention between January 2005 and Dec...

Design, synthesis, and actions of a novel chimeric natriuretic peptide: CD-NP.

Science.gov (United States)

Lisy, Ondrej; Huntley, Brenda K; McCormick, Daniel J; Kurlansky, Paul A; Burnett, John C

2008-07-01

Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides.

B-type natriuretic peptide-guided treatment for heart failure

Science.gov (United States)

McLellan, Julie; Heneghan, Carl J; Perera, Rafael; Clements, Alison M; Glasziou, Paul P; Kearley, Karen E; Pidduck, Nicola; Roberts, Nia W; Tyndel, Sally; Wright, F Lucy; Bankhead, Clare

2016-01-01

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a

Dwarfism and early death in mice lacking C-type natriuretic peptide

Science.gov (United States)

Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

2001-01-01

Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

A candidate liquid chromatography mass spectrometry reference method for the quantification of the cardiac marker 1-32 B-type natriuretic peptide.

Science.gov (United States)

Torma, Attila F; Groves, Kate; Biesenbruch, Sabine; Mussell, Chris; Reid, Alan; Ellison, Steve; Cramer, Rainer; Quaglia, Milena

2017-08-28

B-type natriuretic peptide (BNP) is a 32 amino acid cardiac hormone routinely measured by immunoassays to diagnose heart failure. While it is reported that immunoassay results can vary up to 45%, no attempt of standardization and/or harmonization through the development of certified reference materials (CRMs) or reference measurement procedures (RMPs) has yet been carried out. B-type natriuretic peptide primary calibrator was quantified traceably to the International System of Units (SI) by both amino acid analysis and tryptic digestion. A method for the stabilization of BNP in plasma followed by protein precipitation, solid phase extraction (SPE) and liquid chromatography (LC) mass spectrometry (MS) was then developed and validated for the quantification of BNP at clinically relevant concentrations (15-150 fmol/g). The candidate reference method was applied to the quantification of BNP in a number of samples from the UK NEQAS Cardiac Markers Scheme to demonstrate its applicability to generate reference values and to preliminary evaluate the commutability of a potential CRM. The results from the reference method were consistently lower than the immunoassay results and discrepancy between the immunoassays was observed confirming previous data. The application of the liquid chromatography-mass spectrometry (LC-MS) method to the UK NEQAS samples and the correlation of the results with the immunoassay results shows the potential of the method to support external quality assessment schemes, to improve understanding of the bias of the assays and to establish RMPs for BNP measurements. Furthermore, the method has the potential to be multiplexed for monitoring circulating truncated forms of BNP.

The evolution of the natriuretic peptides - Current applications in human and animal medicine.

Science.gov (United States)

van Kimmenade, Roland R J; Januzzi, James L

2009-05-01

Although natriuretic peptides have played an important role in the fluid homeostasis of vertebrates for over several million years, their importance has only been noticed in the last few decades. Yet, the family of natriuretic peptides have since their discovery, drawn the attention of a broad spectrum of physicians and researchers involved in the maintenance of fluid homeostasis, including marine biologists, basic scientists, physicians and veterinarians. While all natriuretic peptides share a common phylogenetic background, due to differences in receptor-binding affinities, they have evolved into different hormones with clear distinct functions. B-type natriuretic peptide (BNP) is the most studied member of the natriuretic peptide family, and together with its cleavage equivalent amino-terminal proB-type natriuretic peptide (NT-proBNP) these peptides have emerged as important cardiovascular serum markers. However, since their introduction, physicians involved in human or animal medicine have faced common but also different challenges in order to optimally interpret the diagnostic and prognostic value of these novel cardiovascular biomarkers.

Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

DEFF Research Database (Denmark)

Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2011-01-01

The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting that preecla......The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...... that preeclampsia is associated with cardiovascular changes in early pregnancy....

B-Type Natriuretic Peptide: From Posttranslational Processing to Clinical Measurement

DEFF Research Database (Denmark)

Goetze, Jens P

2012-01-01

BACKGROUND:Plasma cardiac natriuretic peptides and peptide fragments from their molecular precursors are markers of heart disease. Clinical studies have defined the current diagnostic utility of these markers, whereas biochemical elucidation of peptide structure and posttranslational processing has...... pathophysiology and capacity. An ongoing characterization of the molecular heterogeneity may not only help us to appreciate the biosynthetic capacity of the endocrine heart but may also lead to the discovery of new and more disease-specific targets for future molecular diagnosis.SUMMARY:Peptides derived from pro...

N-terminal pro-B-type Natriuretic Peptide in three different mechanisms of dysnatremia onset after a child's craniopharyngioma surgery.

Science.gov (United States)

Spatenkova, Vera; Hradil, Jan; Suchomel, Petr

2017-10-01

Craniopharyngioma, due to its sellar location, can be perioperatively complicated by different types of dysnatremia. We present a rare postoperative onset of a combination of three different mechanisms of dysnatremia with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and renal function parameters in a boy with a good outcome after craniopharyngioma surgery: 1/ Central diabetes insipidus (CDI) onset immediately after the operation, hypernatremia with peak serum sodium (SNa) 158 mmol/l) caused by free water polyuria (electrolyte-free water clearance, EWC 0.104 ml/s), NT-proBNP 350 pg/ml; 2/ cerebral salt wasting (CSW) onset on day 7, hyponatremia (SNa 128 mmol/l) with hypoosmolality (measured serum osmolality, SOsm 265 mmol/kg) caused by natriuresis (sodium - daily output 605 mmol/day, fractional excretion 0.035), NT-proBNP 191 pg/ml; 3/ Polydypsia onset on day 11 caused hyponatremia (SNa 132 mmol/l), EWC 0.015, NT-proBNP 68 pg/ml.

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

DEFF Research Database (Denmark)

Christoffersen, Tue E.H.; Aplin, Mark; Strom, Claes C.

2006-01-01

also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system......RNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle....

N-terminal pro B-type natriuretic peptide predicts mortality in patients with left ventricular hypertrophy.

Science.gov (United States)

Garcia, Santiago; Akbar, Muhammad S; Ali, Syed S; Kamdar, Forum; Tsai, Michael Y; Duprez, Daniel A

2010-09-03

Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH. Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records. Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03). NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass. Copyright © 2009 Elsevier B.V. All rights reserved.

Release kinetics of N-terminal pro-B-type natriuretic peptide in a clinical model of acute myocardial infarction.

Science.gov (United States)

Liebetrau, Christoph; Gaede, Luise; Dörr, Oliver; Troidl, Christian; Voss, Sandra; Hoffmann, Jedrzej; Paszko, Agata; Weber, Michael; Rolf, Andreas; Hamm, Christian; Nef, Holger; Möllmann, Helge

2014-02-15

N-terminal segment of B-type natriuretic peptide prohormone (NT-proBNP) is elevated in patients with acute myocardial infarction (AMI) thus providing both diagnostic information and prognostic information. The aim of the present study was to determine the time course of NT-proBNP release in patients undergoing transcoronary ablation of septal hypertrophy (TASH) a procedure mimicking AMI. We analyzed the release kinetics of NT-proBNP in 18 consecutive patients with hypertrophic obstructive cardiomyopathy undergoing TASH. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and 105 min, and 2, 4, 8, and 24h after TASH. NT-proBNP concentrations showed a continuous increase during the first 75 min with a significant percent change compared to baseline value already 15 min after TASH (105.6% [IQR 102.2-112.7]; Pvalue until the 8th h after initiation of myocardial infarction. NT-proBNP concentration increases immediately after induction of myocardial infarction proving early evidence of myocardial injury despite the decrease of the left ventricular wall stress due to the TASH related reduction of the left ventricular outflow gradient. Copyright © 2013 Elsevier B.V. All rights reserved.

Diagnostic Value of N Terminal Pro B Type Natriuretic Peptide (NT-pro BNP in Cardiac Involvement in Patients with Beta- Thalassemia

Directory of Open Access Journals (Sweden)

Noor Mohammad Noori

2017-04-01

Full Text Available Background Heart failure is a major cause of death in thalassemia. The study aimed to determine the diagnostic value of N Terminal Pro B Type Natriuretic Peptide (NT-pro BNP, to early diagnose the cardiac involvement in beta- thalassemia major patients. Materials and Methods  80 thalassemia patients aged 7 to 18 years old (patients group, and 80 healthy age and gender matched controls were enrolled in the case-control study. Patients were selected from those attending to the clinic of Aliasghar hospital, Zahedan-Iran. They were subjected to echo-Doppler tissue and conventional examination for both right and left heart function. Data were analysis using SPSS 18.0 software. Results  NT-pro BNP increased in patients compared the controls (P

Circulating N-terminal fragments of A- and B-type natriuretic peptides: molecular heterogeneity, measurement and clinical application

OpenAIRE

Ala-Kopsala, M. (Minna)

2006-01-01

Abstract Natriuretic peptides have emerged as important candidates for the development of diagnostic tools in cardiovascular disease. Their increased concentrations have been found to be useful for ruling out disease of cardiac origin, as prognostic indicators, and in the follow-up of patients with heart failure. In order for natriuretic peptides to be efficient biomarkers, analytical problems in assay specificity and calibration need to be resolved. The aim of the present study was to elu...

The Informative Value of N-Terminal Pro-type B Natriuretic Peptide in Cardiac Surgical Patients with Hypercreatininemia

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M. G. Burzhunova

2011-01-01

Full Text Available Objective: to study the informative value of a dramatic increase in the preoperative blood level of the inactive moiety of the precursor of N-terminal pro-type B natriuretic peptide (NT-proBNP in cardiac surgical patients with hypercreatininemia. Subjects and materials. Twenty-one patients with a preoperative NT-proBNP level of 1000 pg/ml or more, who underwent myocardial revascularization under extracorporeal circulation (ECC, were examined. The patients were divided into groups with normal (up to 120 ^mol/l (Group 1; n=11 and elevated (Group 2; n=10 creatinine concentrations. The values of circulation were processed after skin incision and at the end of surgery. The clinical features of a perioperative period were analyzed. Results. Creatininemia was 103±3.3 and 183±12.9 ^mol/l in Groups 1 and 2, respectively (p<0.05; NT-proBNP was 1397±139 and 1908±170 pg/ml (p<0.05. EuroSCORE-predicted mortality ran to 9.8±1.6 and 9.1±1.7% (p>0.05. There were no intergroup differences in intraoperative circulatory parameters. The intensity of sympatomimetic therapy after ECC was equal in the identified patient groups and there were either no differences (p>0.05 in the frequency of intra-aortic balloon counterpulsation (18.2 and 10.0%, the length of mechanical ventilation (15±1.5 and 18.7±2.3 hours and intensive care unit stay (1.8±0.5 and 2.0±0.7 days in survivors, and inpatient mortality (23.7 and 20.0% that proved to be substantially higher than the EuroSCORE-predicted one. Regression analysis showed that in the entire group of operated patients, the level of NT-proBNP turned out to be a more significant predictor of inpatient mortality (p=0.012 than EuroSCORE-predicted one (p = 0.04. The similar regularity was characteristic for patients with hypercreatininemia. In the patients with hypercholesterolemia, the EuroSCORE-predicted mortality completely lost its significance (p=0.61 in predicting actual mortality rates. In this group, NT

Sacubitril/valsartan: beyond natriuretic peptides.

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Singh, Jagdeep S S; Burrell, Louise M; Cherif, Myriam; Squire, Iain B; Clark, Andrew L; Lang, Chim C

2017-10-01

Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation

DEFF Research Database (Denmark)

Kristensen, Søren Lund; Jhund, Pardeep S; Mogensen, Ulrik M

2017-01-01

BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients...... Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095......-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without (PHeart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30...

Implication of C-type natriuretic peptide-3 signaling in glycosaminoglycan synthesis and chondrocyte hypertrophy during TGF-β1 induced chondrogenic differentiation of chicken bone marrow-derived mesenchymal stem cells.

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Kocamaz, Erdogan; Gok, Duygu; Cetinkaya, Ayse; Tufan, A Cevik

2012-10-01

This study investigated the involvement of CNP-3, chick homologue for human C-type natriuretic peptide (CNP), in TGF-β1 induced chondrogenic differentiation of chicken bone marrow-derived mesenchymal stem cells (MSCs). Chondrogenic differentiation of MSCs in pellet cultures was induced by TGF-β1. Chondrogenic differentiation and glycosaminoglycan synthesis were analyzed on the basis of basic histology, collagen type II expression, and Alcian blue staining. Antibodies against CNP and NPR-B were used to block their function during these processes. Results revealed that expression of CNP-3 and NPR-B in MSCs were regulated by TGF-β1 in monolayer cultures at mRNA level. In pellet cultures of MSCs, TGF-β1 successfully induced chondrogenic differentiation and glycosaminoglycan synthesis. Addition of CNP into the TGF-β1 supplemented chondrogenic differentiation medium further induced the glycosaminoglycan synthesis and hypertrophy of differentiated chondrocytes in these pellets. Pellets induced with TGF-β1 and treated with antibodies against CNP and NPR-B, did show collagen type II expression, however, Alcian blue staining showing glycosaminoglycan synthesis was significantly suppressed. In conclusion, CNP-3/NPR-B signaling may strongly be involved in synthesis of glycosaminoglycans of the chondrogenic matrix and hypertrophy of differentiated chondrocytes during TGF-β1 induced chondrogenic differentiation of MSCs.

Breed differences in natriuretic peptides in healthy dogs

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Sjöstrand, K.; Wess, G.; Ljungvall, I.

2014-01-01

BACKGROUND: Measurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor. OBJECTIVE: To investigate breed...... variation in plasma concentrations of pro-atrial natriuretic peptide 31-67 (proANP 31-67) and N-terminal B-type natriuretic peptide (NT-proBNP) in healthy dogs. ANIMALS: 535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project. METHODS: Absence...... the median concentration in Doberman Pinschers. CONCLUSIONS AND CLINICAL IMPORTANCE: Considerable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT-proBNP. Additional studies are needed to establish breed...

Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

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Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2011-01-01

The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...... that preeclampsia is associated with cardiovascular changes in early pregnancy....

[B-type natriuretic peptide assessment in the diagnosis of rejection after pediatric heart transplant].

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Sylos, Cristina de; Azeka, Estela; Kajita, Luis; Benvenutti, Luis; Strunz, Célia Cassaro; Branco, Klébia Castello; Riso, Arlindo Almeida; Tanamati, Carla; Jatene, Marcelo; Barbero-Marcial, Miguel

2009-03-01

Rejection is one of the major causes of mortality following pediatric heart transplant. B-type natriuretic peptide (BNP) has been studied as a method for the diagnosis of acute rejection, especially in adult patients undergoing heart transplant. To correlate serum BNP levels with acute rejection as diagnosed by endomyocardial biopsy in patients of the pediatric heart transplant group. A total of 50 BNP samples were collected from 33 children in the postoperative period of heart transplant, and data on age, gender, skin color, blood group, immune panel, follow-up time after transplant, functional class, immunosuppressive regimen used and number of rejections were analyzed. Thirty three children with median age of 10.13 years were analyzed; of these, 54% were females and 78% were Caucasians. BNP levels were determined at a mean time from transplant of 4.25 years. Nine episodes of rejection were diagnosed in eight patients (27%) by means of endomyocardial biopsy; of these, three were grade 3A, five were grade 2, and one had humoral rejection. At the moment of biopsy, most patients were asymptomatic. The mean serum BNP level was 77.18 pg/ml, with 144.22 pg/ml in the group with rejection and 62.46 pg/ml in the group without rejection, with p = 0.02. Asymptomatic children can present acute rejection in the postoperative period of heart transplant. Serum BNP levels show a statistically significant difference in the group with rejection and thus can be an additional method in the diagnosis of cardiac rejection.

B-type natriuretic peptide (BNP serum levels in rats after forced repeated swimming stress

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Almira Hadžovic-Džuvo

2011-02-01

Full Text Available Aim To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. Methods Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n =8 and stress group (n =8. Rats in the stress group were exposed to forced swimming stress daily, for 7 days. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep containing tap water (temperature ca. 25°C. The depth of water was 40 cm. Duration of each swimming session progressively increased from 10 minutes on the irst day to 40 minutes on days 6 and 7. Rats were sacriiced and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.. Results There was no statistically signiicant difference between mean BNP serum level in the stress group after the swimming period (0.81±0.14 ng/ml as compared to the unstressed group of rats (0.8 ±0.08ng/ml. After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs.272.8 g, but this difference was not statistically signiicant. The stress period had no inluence on food intake in the stress rat group. Conclusion The workload consisting of 40-minutes long swimming session is not suficient to provoke BNP release from myocardium in rats.

B-type natriuretic peptide (BNP) serum levels in rats after forced repeated swimming stress.

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Hadzovic-Dzuvo, Almira; Valjevac, Amina; Avdagić, Nesina; Lepara, Orhan; Zaćiragić, Asija; Jadrić, Radivoj; Alajbegović, Jasmin; Prnjavorac, Besim

2011-02-01

To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n = 8) and stress group (n = 8). Rats in the stress group were exposed to forced swimming stress daily, for 7 days. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep) containing tap water (temperature ca. 25 degrees C). The depth of water was 40 cm. Duration of each swimming session progressively increased from 10 minutes on the first day to 40 minutes on days 6 and 7. Rats were sacrificed and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.). There was no statistically significant difference between mean BNP serum level in the stress group after the swimming period (0.81 +/- 0.14 ng/ml) as compared to the unstressed group of rats (0.8 +/- 0.08 ng/ml). After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs. 272.8 g), but this difference was not statistically significant. The stress period had no influence on food intake in the stress rat group. The workload consisting of 40-minutes long swimming session is not sufficient to provoke BNP release from myocardium in rats.

Relative Importance of History of Heart Failure Hospitalization and N-Terminal Pro-B-Type Natriuretic Peptide Level as Predictors of Outcomes in Patients With Heart Failure and Preserved Ejection Fraction

DEFF Research Database (Denmark)

Kristensen, Søren L; Jhund, Pardeep S; Køber, Lars

2015-01-01

of NT-proBNP (n = 1468) (HR: 3.19; 95% CI: 2.68 to 3.80). In patients with no recent HF hospitalization and NT-proBNP ≤360 pg/ml (n = 1,187), the event rate was 2.43 (95% CI: 2.03 to 2.90) compared with 17.79 (95% CI: 15.77 to 20.07) per 100 person-years when both risk predictors were present (n = 523......; HR: 6.18; 95% CI: 4.96 to 7.69). CONCLUSIONS: Recent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present.......OBJECTIVES: The aim of this study was to investigate N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and recent heart failure (HF) hospitalization as predictors of future events in heart failure - preserved ejection fraction (HF-PEF). BACKGROUND: Recently, doubt has been expressed...

N-Terminal Pro–B-Type Natriuretic Peptide Variability in Stable Dialysis Patients

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Hayen, Andrew; Horvath, Andrea R.; Dimeski, Goce; Coburn, Amanda; Johnson, David W.; Hawley, Carmel M.; Campbell, Scott B.; Craig, Jonathan C.

2015-01-01

Background and objectives Monitoring N-terminal pro–B-type natriuretic peptide (NT-proBNP) may be useful for assessing cardiovascular risk in dialysis patients. However, its biologic variation is unknown, hindering the accurate interpretation of serial concentrations. The aims of this prospective cohort study were to estimate the within- and between-person coefficients of variation of NT-proBNP in stable dialysis patients, and derive the critical difference between measurements needed to exclude biologic and analytic variation. Design, setting, participants, & measurements Fifty-five prevalent hemodialysis and peritoneal dialysis patients attending two hospitals were assessed weekly for 5 weeks and then monthly for 4 months between October 2010 and April 2012. Assessments were conducted at the same time in the dialysis cycle and entailed NT-proBNP testing, clinical review, electrocardiography, and bioimpedance spectroscopy. Patients were excluded if they became unstable. Results This study analyzed 136 weekly and 113 monthly NT-proBNP measurements from 40 and 41 stable patients, respectively. Results showed that 22% had ischemic heart disease; 9% and 87% had left ventricular systolic and diastolic dysfunction, respectively. Respective between- and within-person coefficients of variation were 153% and 27% for weekly measurements, and 148% and 35% for monthly measurements. Within-person variation was unaffected by dialysis modality, hydration status, inflammation, or cardiac comorbidity. NT-proBNP concentrations measured at weekly intervals needed to increase by at least 46% or decrease by 84% to exclude change due to biologic and analytic variation alone with 90% certainty, whereas monthly measurements needed to increase by at least 119% or decrease by 54%. Conclusions The between-person variation of NT-proBNP was large and markedly greater than within-person variation, indicating that NT-proBNP testing might better be applied in the dialysis population using a

N-terminal pro-B-type natriuretic peptide variability in stable dialysis patients.

Science.gov (United States)

Fahim, Magid A; Hayen, Andrew; Horvath, Andrea R; Dimeski, Goce; Coburn, Amanda; Johnson, David W; Hawley, Carmel M; Campbell, Scott B; Craig, Jonathan C

2015-04-07

Monitoring N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful for assessing cardiovascular risk in dialysis patients. However, its biologic variation is unknown, hindering the accurate interpretation of serial concentrations. The aims of this prospective cohort study were to estimate the within- and between-person coefficients of variation of NT-proBNP in stable dialysis patients, and derive the critical difference between measurements needed to exclude biologic and analytic variation. Fifty-five prevalent hemodialysis and peritoneal dialysis patients attending two hospitals were assessed weekly for 5 weeks and then monthly for 4 months between October 2010 and April 2012. Assessments were conducted at the same time in the dialysis cycle and entailed NT-proBNP testing, clinical review, electrocardiography, and bioimpedance spectroscopy. Patients were excluded if they became unstable. This study analyzed 136 weekly and 113 monthly NT-proBNP measurements from 40 and 41 stable patients, respectively. Results showed that 22% had ischemic heart disease; 9% and 87% had left ventricular systolic and diastolic dysfunction, respectively. Respective between- and within-person coefficients of variation were 153% and 27% for weekly measurements, and 148% and 35% for monthly measurements. Within-person variation was unaffected by dialysis modality, hydration status, inflammation, or cardiac comorbidity. NT-proBNP concentrations measured at weekly intervals needed to increase by at least 46% or decrease by 84% to exclude change due to biologic and analytic variation alone with 90% certainty, whereas monthly measurements needed to increase by at least 119% or decrease by 54%. The between-person variation of NT-proBNP was large and markedly greater than within-person variation, indicating that NT-proBNP testing might better be applied in the dialysis population using a relative-change strategy. Serial NT-proBNP concentrations need to double or halve to confidently

Natriuretic peptides in cardiometabolic regulation and disease

DEFF Research Database (Denmark)

Zois, Nora E; Bartels, Emil D; Hunter, Ingrid

2014-01-01

decade. Dysregulation of the natriuretic peptide system has been associated with obesity, glucose intolerance, type 2 diabetes mellitus, and essential hypertension. Moreover, the natriuretic peptides have been implicated in the protection against atherosclerosis, thrombosis, and myocardial ischaemia. All...... these conditions can coexist and potentially lead to heart failure, a syndrome associated with a functional natriuretic peptide deficiency despite high circulating concentrations of immunoreactive peptides. Therefore, dysregulation of the natriuretic peptide system, a 'natriuretic handicap', might be an important...... factor in the initiation and progression of metabolic dysfunction and its accompanying cardiovascular complications. This Review provides a summary of the natriuretic peptide system and its involvement in these cardiometabolic conditions. We propose that these peptides might have an integrating role...

[The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery].

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Baysal, Ayse; Saşmazel, Ahmet; Yildirim, Ayse; Ozyaprak, Buket; Gundogus, Narin; Kocak, Tuncer

2014-01-01

In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48h after operation. The patients enrolled into the study were divided into two groups depending on: (1) Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2) Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1) duration of mechanical ventilation ≥72h, (2) intensive care unit stay >7days, and (3) mortality. The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n=35, n=16, respectively) showed significant differences in repeated measurement time points (p=0.0001). The preoperative brain natriuretic peptide cut-off value of 125.5pgmL-1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r=0.67, p=0.0001). In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5pgmL-1 are at risk of developing low cardiac output syndrome which is an important postoperative outcome. Copyright © 2013 Sociedade

The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery

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Ayse Baysal

2014-09-01

Full Text Available Background and objectives: In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. Methods: In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48 h after operation. The patients enrolled into the study were divided into two groups depending on: (1 Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2 Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1 duration of mechanical ventilation ≥72 h, (2 intensive care unit stay >7days, and (3 mortality. Results: The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n = 35, n = 16, respectively showed significant differences in repeated measurement time points (p = 0.0001. The preoperative brain natriuretic peptide cut-off value of 125.5 pg mL−1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r = 0.67, p = 0.0001. Conclusions: In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5 pg mL−1 are at risk of developing low cardiac

Plasma N-terminal pro B-type natriuretic peptide concentrations in dogs with pulmonic stenosis.

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Kobayashi, Keiya; Hori, Yasutomo; Chimura, Syuuichi

2014-06-01

The detailed information between plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations and dogs with pulmonic stenosis (PS) is still unknown. The aim of the present study was to investigate the clinical utility of measuring plasma NT-proBNP concentrations in dogs with PS and to determine whether plasma NT-proBNP concentration could be used to assess disease severity. This retrospective study enrolled 30 client-owned, untreated dogs with PS (asymptomatic [n=23] and symptomatic [n=7]) and 11 healthy laboratory beagles. Results of physical examination, thoracic radiography and echocardiography were recorded. Plasma NT-proBNP concentrations were measured using commercial laboratories. Compared to the healthy control dogs, cardiothoracic ratio was significantly increased in dogs with both asymptomatic and symptomatic PS. Similarly, the ratio of the main pulmonary artery to aorta was significantly decreased in dogs with both asymptomatic and symptomatic PS. The pulmonic pressure gradient in the symptomatic PS dogs was significantly higher than that in the asymptomatic PS dogs. Plasma NT-proBNP concentration was significantly elevated in the symptomatic PS dogs compared to the healthy control dogs and the asymptomatic PS dogs. Furthermore, the Doppler-derived pulmonic pressure gradient was significantly correlated with the plasma NT-proBNP concentration (r=0.78, r(2)=0.61, P764 pmol/l to identify severe PS had a sensitivity of 76.2% and specificity of 81.8%. The plasma NT-proBNP concentration increased by spontaneous PS, i.e. right-sided pressure overload and can be used as an additional method to assess the severity of PS in dogs.

B-type natriuretic peptide as a marker for heart failure in patients with acute stroke.

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Koenig, Matthew A; Puttgen, H Adrian; Prabhakaran, Vivek; Reich, Daniel; Stevens, Robert D

2007-09-01

To determine whether serum N-terminal pro-B-type natriuretic peptide (N-BNP), a biomarker of myocardial wall stress, is specific to acute heart failure (HF) in patients hospitalized with stroke. Case-control study. Tertiary hospital, Neurosciences Critical Care Unit and Stroke Unit. Consecutive patients with acute ischemic or hemorrhagic stroke who were evaluated for HF. None. Cases and controls were classified, respectively, as patients with or without HF, defined according to modified Framingham criteria. Seventy-two patients were evaluated, 39 with ischemic stroke, 22 with aneurysmal subarachnoid hemorrhage (SAH), and 11 with intracerebral hemorrhage (ICH). Thirty-four patients (47%) met criteria for HF, and 47 patients (65%) had systolic or diastolic left ventricular (LV) dysfunction on echocardiogram. Serum N-BNP was measured a median of 48 h following the onset of stroke and was increased (> 900 pg/ml) in 56 patients (78%), with higher levels in non-survivors (11898 +/- 12741 vs 4073 +/-5691; p = 0.001). In a multiple regression model, N-BNP elevation was not independently associated with HF (OR 5.4, 95% CI 0.8-36.0, p = 0.084). At a cut-off of 900 pg/ml, the sensitivity of N-BNP for HF was 94%, specificity 37%, positive predictive value (PPV) 57%, and negative predictive value (NPV) 88%. For systolic or diastolic LV dysfunction, the sensitivity of N-BNP was 89%, specificity 44%, PPV 75%, and NPV 69%. These results demonstrate that N-BNP elevation is not specific to HF or LV dysfunction in patients with acute ischemic stroke, SAH, and ICH.

Effects of oral contraceptives on natriuretic peptide levels in women with hypothalamic amenorrhea: a pilot study.

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Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K

2011-06-30

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60%-75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives (OC) increases natriuretic peptide levels and that end-of-study free T levels are inversely associated with amino-terminal pro-B-type natriuretic peptide levels, consistent with the hypothesis that natriuretic peptide levels may be mediated by differences in gonadal steroid concentrations-estrogens (E) or androgens. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Clinically relevant diagnostic research in primary care: the example of B-type natriuretic peptides in the detection of heart failure.

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Kelder, Johannes C; Rutten, Frans H; Hoes, Arno W

2009-02-01

With the emergence of novel diagnostic tests, e.g. point-of-care tests, clinically relevant empirical evidence is needed to assess whether such a test should be used in daily practice. With the example of the value of B-type natriuretic peptides (BNP) in the diagnostic assessment of suspected heart failure, we will discuss the major methodological issues crucial in diagnostic research; most notably the choice of the study population and the data analysis with a multivariable approach. BNP have been studied extensively in the emergency care setting, and also several studies in the primary care are available. The usefulness of this test when applied in combination with other readily available tests is still not adequately addressed in the relevant patient domain, i.e. those who are clinically suspected of heart failure by their GP. Future diagnostic research in primary care should be targeted much more at answering the clinically relevant question 'Is it useful to add this (new) test to the other tests I usually perform, including history taking and physical examination, in patients I suspect of having a certain disease'.

[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].

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Castro, A; Dias, P; Pereira, M; Pimenta, J; Friões, F; Rodrigues, R; Ferreira, A; Bettencourt, P

2001-11-01

Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. Prospective study. One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.

N-Terminal Pro-B Type Natriuretic Peptide is Associated with Mild Cognitive Impairment in the General Population.

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Kara, Kaffer; Mahabadi, Amir Abbas; Weimar, Christian; Winkler, Angela; Neumann, Till; Kälsch, Hagen; Dragano, Nico; Moebus, Susanne; Erbel, Raimund; Jöckel, Karl-Heinz; Jokisch, Martha

2017-01-01

N-terminal pro-B type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and is linked with silent cardiac diseases. While associations of cognitive impairment with manifest cardiovascular diseases are established, data on whether subclinical elevation of NT-proBNP levels below clinically established threshold of heart failure is related with cognitive functioning, especially mild cognitive impairment (MCI), is rare. Aim of the present study was to investigate the cross-sectional association of NT-proBNP levels and MCI in a population-based study sample without heart failure. We used data from the second examination of the population based Heinz-Nixdorf-Recall-Study. Subjects with overt coronary heart disease and subjects with NT-proBNP levels indicating potential heart failure (NT-proBNP≥300 pg/ml) were excluded from this analysis. Participants performed a validated brief cognitive assessment and were classified either as MCI [subtypes: amnestic-MCI (aMCI), non-amnestic-MCI (naMCI)], or cognitively-normal. We included 419 participants with MCI (63.1±7.4 y; 47% men; aMCI n = 209; naMCI n = 210) and 1,206 cognitively normal participants (62.42±7.1 y; 48% men). NT-proBNP-levels≥125 pg/ml compared to heart failure, higher NT-proBNPlevels are associated with MCI and both MCI subtypes independent of traditional cardiovascular risk factors and sociodemographic parameters.

C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

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Olney, Robert C; Prickett, Timothy C R; Espiner, Eric A; Mackenzie, William G; Duker, Angela L; Ditro, Colleen; Zabel, Bernhard; Hasegawa, Tomonobu; Kitoh, Hiroshi; Aylsworth, Arthur S; Bober, Michael B

2015-02-01

C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor (natriuretic peptide receptor-B [NPR-B]), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in overactivation of the MEK/ERK MAPK pathway. The purpose of this study was to determine whether these syndromes exhibit evidence of CNP resistance as reflected by increases in plasma CNP and its amino-terminal propeptide (NTproCNP). This was a prospective, observational study. Participants were 63 children and 20 adults with achondroplasia, 6 children with hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1 adult with AMDM. Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDSs) of 1.0 (0.3-1.4) (median [interquartile range]) and NTproCNP SDSs of 1.4 (0.4-1.8; P achondroplasia (CNP SDSs of 1.5 [0.7-2.1] and NTproCNP SDSs of 0.5 [0.1-1.0], P < .005). In children with hypochondroplasia, CNP SDSs were 1.3 (0.7-1.5) (P = .08) and NTproCNP SDSs were 1.9 (1.8-2.3) (P < .05). In children with AMDM, CNP SDSs were 1.6 (1.4-3.3) and NTproCNP SDSs were 4.2 (2.7-6.2) (P < .01). In these skeletal dysplasias, elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP.

Plasma B-type natriuretic peptide concentration for diagnosis of acute heart failure with renal insufficiency

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Naila Atik Khan

2016-07-01

Full Text Available Background : Plasma B-type natriuretic peptide (BNP is the diagnostic tool for acute heart failure (AHF.This natriu­retic peptide level depends on renal function, through renal metabolism and excretion. Therefore we examined the effect ofrenal impairment on plasma BNP level during diagnosis of AHF.Objective: The objective of the study was to assess the effect of renal dysfunction on plasma BNP level and to determine appropriate cutoff value of plasma BNP to diagnose the patients of AHF with renal insufficiency.Methods: This cross sectional analytical study was conducted in the Depart­ment of Biochemistry Bangabandhu Sheikh Mujib Medical University (BSMMU. The study was done among 90 AHF patients selected from cardiology emergency department during the period of July 2012 to June 2013. After enrollment plasma BNP concentration was measured and eGFR was estimated from serum creatinine by the four parameter Modifica­tion of Diet and Renal Disease (MORD equation and then grouped into two groups on the basis of empirical cut off value of eGFR 60 ml/min/1.73 m2Results: In this study a significant negative correlation was found between plasma BNP evel and eGFR (P<0.001 , with higher BNP levels observed as eGFR declined. The optimal BNP cutoff value for diagno­sis of AHF patients with renal insufficiency was 824 pg/ml. At this cutoff level AHF with renal insufficiency could be diagnosed with sensitivity and specificity of 84% and 71 %, respectively.Conclusions: By adjusting the cutoff value, plasma BNP can be used to diagnose AHF with renal insufficiency with an acceptable sensitivity and specificity.

Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure

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Fu, Shihui; Ping, Ping; Wang, Fengqi; Luo, Leiming

2018-01-01

As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB...

Efficacy of B-Type Natriuretic Peptide Is Coupled to Phosphodiesterase 2A in Cardiac Sympathetic Neurons.

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Li, Dan; Lu, Chieh-Ju; Hao, Guoliang; Wright, Hannah; Woodward, Lavinia; Liu, Kun; Vergari, Elisa; Surdo, Nicoletta C; Herring, Neil; Zaccolo, Manuela; Paterson, David J

2015-07-01

Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP. Because phosphodiesterase activity is altered in cardiovascular disease, we tested the hypothesis that BNP might lose its efficacy by minimizing the action of cGMP on downstream pathways coupled to neurotransmission. BNP decreased norepinephrine release from atrial preparations in response to field stimulation and also significantly reduced the heart rate responses to sympathetic nerve stimulation in vitro. Using electrophysiological recording and fluorescence imaging, BNP also reduced the depolarization evoked calcium current and intracellular calcium transient in isolated cardiac sympathetic neurons. Pharmacological manipulations suggested that the reduction in the calcium transient was regulated by a cGMP/protein kinase G pathway. Fluorescence resonance energy transfer measurements for cAMP, and an immunoassay for cGMP, showed that BNP increased cGMP, but not cAMP. In addition, overexpression of phosphodiesterase 2A after adenoviral gene transfer markedly decreased BNP stimulation of cGMP and abrogated the BNP responses to the calcium current, intracellular calcium transient, and neurotransmitter release. These effects were reversed on inhibition of phosphodiesterase 2A. Moreover, phosphodiesterase 2A activity was significantly elevated in stellate neurons from the prohypertensive rat compared with the normotensive control. Our data suggest that abnormally high levels of phosphodiesterase 2A may provide a brake against the inhibitory action of BNP on sympathetic transmission. © 2015 American Heart Association, Inc.

Cocoa flavanols reduce N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure.

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De Palma, Rodney; Sotto, Imelda; Wood, Elizabeth G; Khan, Noorafza Q; Butler, Jane; Johnston, Atholl; Rothman, Martin T; Corder, Roger

2016-06-01

Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an index of improved cardiac function. Thirty-two patients with chronic HF, stable on guideline-directed medical therapy, were randomized to consume 50 g/day of high-flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low-flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty-four patients completed the study. After 4 weeks of HFDC, NT-proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (-44 ± 69%), LFDC (-33 ± 72%), and follow-up (-41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (-6.7 ± 10.1 mmHg). Reductions in blood pressure and NT-proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF.

Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet

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Goncalves, Gleisy Kelly; de Oliveira, Thiago Henrique Caldeira; de Oliveira Belo, Najara

2017-01-01

Background Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. Material/Methods Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. Results A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. Conclusions The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model. PMID:29249795

Prognostic value of natriuretic peptides in severe trauma patients with multiple organ dysfunction syndrome

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LI, NAN; SONG, ZHI; WANG, JING; TENG, YUE; CUI, YAN; JIN, HONGXU; GAO, YAN

2015-01-01

The aim of the present study was to evaluate the prognostic values of the N-terminal peptide of pro-atrial natriuretic peptide (NT-proANP) and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) in severe trauma patients developing multiple organ dysfunction syndrome (MODS). Out of the 126 severe trauma patients that were admitted to the Emergency Intensive Care Unit of the General Hospital of Shenyang Military Region between January 2009 and December 2011, 26 patients with mult...

Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart.

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Izgut-Uysal, Vecihe Nimet; Acar, Nuray; Birsen, Ilknur; Ozcan, Filiz; Ozbey, Ozlem; Soylu, Hakan; Avci, Sema; Tepekoy, Filiz; Akkoyunlu, Gokhan; Yucel, Gultekin; Ustunel, Ismail

2018-04-01

The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urinary osteocalcin and serum pro-C-type natriuretic peptide predict linear catch-up growth in infants

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Kilpeläinen, Leena; Ivaska, Kaisa K; Kuiri-Hänninen, Tanja

2012-01-01

of this longitudinal study was to determine the extent to which postnatal levels of circulating cartilage (serum pro-C-type natriuretic peptide [S-proCNP]) and urinary bone metabolic markers (urinary osteocalcin [MidOC] and two forms of C-terminal cross-linked telopeptide of type I collagen [U-α-CTX-I and U...

The evaluation of B-type Natriuretic Peptide and Troponin I in acute myocardial infarction and unstable angina

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Nafija Serdarevic

2014-09-01

Full Text Available Introduction: The diagnostic utility of B-type natriuretic peptide (BNP has prompted interest in its use as an aid in the detection of early heart failure and assessment of diseases. The first objective of this study was measurement of BNP and troponin I (TnI blood levels in patients with acute myocardial infarction (AMI and unstable angina. The second objective of this study was to find a correlation between TnI and BNP in blood.Methods: The concentrations of BNP and TnI in 150 blood levels were determined using CMIA (chemiluminescent microparticle immunoassay Architect and 2000 (Abbott diagnostics. The retrospective study included 100 patients who were hospitalized at the Department of Internal Medicine of the University Clinical Center Sarajevo and 50 healthy control. The reference blood range of BNP is 0-100 pg/mL and TnI is 0.00-0.4 ng/mL.Results: In the patients with AMI the mean value of BNP is 764.48 ± 639.52 pg/mL and TnI is 2.50 ± 2.28ng/mL. The patients with unstable angina have BNP 287.18 ± 593.20 pg/mL and TnI 0.10 ± 0.23 ng/mL. Our studies have shown that the correlation between BNP and TnI was statistically significant for p< 0.05 using Student t test with correlation coefficient r = 0.36. Conclusions: BNP and TnI levels can help to identify the patients with a high risk for cardiovascular diseases.

Natriuretic peptides and integrated risk assessment for cardiovascular disease

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Willeit, Peter; Kaptoge, S; Welsh, P.

2016-01-01

samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes......BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present...... by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored...

Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

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Misono, K. S.; Philo, J. S.; Arakawa, T.; Ogata, C. M.; Qiu, Y.; Ogawa, H.; Young, H. S. (Biosciences Division); (Univ. of Nevada); (Alliance Protein Labs.)

2011-06-01

Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.

Reference intervals for N-terminal pro-B-type natriuretic peptide in amniotic fluid between 10 and 34 weeks of gestation.

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Waltraut M Merz

Full Text Available BACKGROUND: In adult and pediatric cardiology, n-terminal pro-B-type natriuretic peptide (nt-proBNP serves as biomarker in the diagnosis and management of cardiovascular dysfunction. Elevated levels of circulating nt-proBNP are present in fetal conditions associated with myocardial pressure or volume load. Compared to fetal blood sampling, amniocentesis is technically easier and can be performed from early pregnancy onwards. We aimed to investigate amniotic fluid (AF nt-proBNP concentrations in normal pregnancies between 10 and 34 weeks of gestation. METHODS: Nt-proBNP and total protein (TP was measured in AF by chemiluminescence assay (photometry, respectively. To adjust for a potential dilutional effect, the AF-nt-proBNP/AF-TP ratio was analyzed. Reference intervals were constructed by regression modeling across gestational age. RESULTS: 132 samples were analyzed. A negative correlation between AF-nt-proBNP/AF-TP ratio and gestational age was observed. Curves for the mean and the 5% and 95% reference interval between 10 and 34 weeks of gestation were established. CONCLUSION: In normal pregnancy, nt-proBNP is present in AF and decreases during gestation. Our data provide the basis for research on AF-nt-proBNP as biomarker in fetal medicine.

Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

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Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

2014-01-01

Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6, and improves central hemodynamics in severe heart failure patients.

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Kyrzopoulos, Stamos; Adamopoulos, Stamatis; Parissis, John T; Rassias, John; Kostakis, George; Iliodromitis, Efstathios; Degiannis, Dimitrios; Kremastinos, Dimitrios Th

2005-03-30

Plasma B-type natriuretic peptide (BNP) and interleukin 6 (IL-6) levels have recently been demonstrated as significant neurohormonal markers associated with the progression of chronic heart failure (CHF). Additionally, clinical studies have shown that the calcium sensitizer, levosimendan, beneficially affects the central hemodynamics of CHF patients and improves their long-term prognosis. This study investigates whether levosimendan-induced hemodynamic improvement of CHF patients is related to the respective changes of NT-proBNP and IL-6 levels. Circulating levels of NT-pro BNP and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 12 patients with decompensated advanced CHF at baseline, immediately after the end of a 24-h levosimendan infusion and 72 h after the initiation of treatment. Hemodynamic parameters of patients (pulmonary wedge and pulmonary artery pressure (PAP), systemic and pulmonary vascular resistance (PVR), stroke volume, and cardiac output and index) were also monitored during the same period. NT-proBNP and IL-6 levels were significantly reduced in severe CHF patients within 72 h after the initiation of levosimendan treatment (pNT-proBNP levels and the respective reduction of pulmonary wedge pressure (r(s)=0.65, pBNP and IL-6 levels may be useful biochemical markers related with the levosimendan-induced improvement in central hemodynamics and the clinical status of decompensated advanced CHF patients.

Comparability of Results Between a Point-of-Care and an Automated Instrument for Measurement of B-Type Natriuretic Peptide

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Shah, Kevin

2010-02-01

Full Text Available Objectives: Heart failure is one of the leading causes of death in the U.S. The incorporation of B-type natriuretic peptide (BNP measurements when triaging patients presenting with shortness of breath has improved the diagnostic and prognostic ability of physicians. Currently, there are no point-of-care systems for quantifying BNP that can be used without sacrificing accuracy. We compared the analytical performance of the Abbott i-STAT analyzer, a handheld point-of-care system for measuring BNP, with the lab-based system, the Abbott ARCHITECT.Methods: One-hundred fifty samples were collected from three clinical settings: 41 from the Emergency Department, 58 from the inpatient wards, and 51 from heart failure outpatient clinics. Linear regression and bias difference analyses were run to evaluate the accuracy of the i-STAT. Correlation between the i-STAT and Architect BNP values were made with values of BNP.Results: The correlation coefficient was r=0.977 (N=150, p<.0001. The average bias was significant (-36 and there were concentration-dependent differences at higher BNP values. Precision of the i-STAT was poor compared to the lab-based platform.Conclusion: Although the precision of the i-STAT was poor, there was good clinical agreement between the i-STAT and the lab-based platform. [West J Emerg Med. 2010; 11(1:44-48].

In-hospital and long-term outcomes of congestive heart failure: Predictive value of B-type and amino-terminal pro-B-type natriuretic peptides and their ratio.

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Dai, Yuxiang; Yang, Jun; Takagi, Atsutoshi; Konishi, Hakuoh; Miyazaki, Tetsuro; Masuda, Hiroshi; Shimada, Kazunori; Miyauchi, Katsumi; Daida, Hiroyuki

2017-08-01

Relative changes in B-type natriuretic peptide (BNP) and amino terminal pro-BNP (NT-proBNP) levels may help to assess the risk of congestive heart failure (CHF). However, whether these levels at the time of admission enable the prediction of outcomes with acute exacerbation remains unknown. The current study determined the abilities of BNP, NT-proBNP and their ratio to predict in-hospital and long-term outcomes of patients with CHF. Patients who were admitted to the cardiac care unit of Juntendo University Hospital (Tokyo, Japan) with acute CHF onset were consecutively enrolled into the present observational study. Serum levels of BNP and NT-proBNP were immediately measured on admission, and other biomarkers and clinical data were also investigated. Of 195 enrolled patients, 16 (8.2%) succumbed to CHF in hospital and 124 (69.3%) reached the endpoint of mortality or readmission following a median follow-up of 14 months. Multiple linear regression analysis revealed body mass index, low density lipoprotein cholesterol, hemoglobin, estimated glomerular filtration rate and C-reactive protein as independent predictors of the NT-proBNP/BNP ratio. BNP, NT-proBNP and their ratio were significantly higher among those who succumbed to CHF than in those who remained alive in hospital (P<0.05). Logistic regression analysis indicated that the ratio was an independent predictor for in-hospital mortality and long-term outcomes. In conclusion, the ratio of NT-proBNP to BNP more effectively predicts in-hospital outcomes than either factor alone and it may also help to predict outcomes among patients with acute exacerbation of HF.

[The role of natriuretic peptides in heart failure].

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Ancona, R; Limongelli, G; Pacileo, G; Miele, T; Rea, A; Roselli, T; Masarone, D; Messina, S; Palmieri, R; Golia, E; Iacomino, M; Gala, S; Calabrò, P; Di Salvo, G; Calabrò, R

2007-10-01

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Impairment of the natriuretic peptide system in follitropin receptor knockout mice and reversal by estradiol: implications for obesity-associated hypertension in menopause.

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Belo, Najara O; Sairam, M Ram; Dos Reis, Adelina M

2008-03-01

Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.

Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity

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Kistorp, Caroline Michaela Nervil; Bliddal, Henning; Gøtze, Jens P.

2014-01-01

BACKGROUND: Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations...... of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). RESULTS: A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal...

Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

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Essam M Abdelalim

2016-12-01

Full Text Available Brain natriuretic peptide (BNP exerts its functions through natriuretic peptide receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using RT-PCR and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and DRG. BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the dorsal horn of the spinal cord and in the neurons of the intermediate column and ventral horn. Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I-II labeled with calcitonin gene-related peptide (CGRP, suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase in the motor neurons of the ventral horn. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NPR-A and/or NPR-B in the DRG and spinal cord.

Changes in Serum Natriuretic Peptide Levels after Percutaneous Closure of Small to Moderate Ventricular Septal Defects

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Yuksel Kaya

2012-01-01

Full Text Available Background. B-type natriuretic peptide has been shown to be a very sensitive and specific marker of heart failure. In this study, we aimed to investigate the effect of percutaneous closure of ventricular septal defects with Amplatzer septal occluders on brain natriuretic peptide levels. Methods. Between 2008 and 2011, 23 patients underwent successfully percutaneous ventricular septal defect closure in 4 cardiology centers. Brain natriuretic peptide levels were measured in nine patients (4 male, mean ages were 25.3±14.3 who underwent percutaneous closure with Amplatzer occluders for membranous or muscular ventricular septal defects were enrolled in the study. Brain natriuretic peptide levels were measured one day before and one month after the closure. Patients were evaluated clinically and by echocardiography one month after the procedure. Results. Percutaneous closures of ventricular septal defects were successfully performed in all patients. There was not any significant adverse event in patients group during followup. Decrease in brain natriuretic peptide levels after closure were statistically significant (97.3±78.6 versus 26.8±15.6, =0.013. Conclusion. Brain Natriuretic Peptide levels are elevated in patients with ventricular septal defects as compared to controls. Percutaneous closure of Ventricular Septal Defect with Amplatzer occluders decreases the BNP levels.

Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

Directory of Open Access Journals (Sweden)

Roman Pfister

2011-10-01

Full Text Available Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP levels in blood and risk of type 2 diabetes (T2D, but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36% decreased risk of incident T2D per one standard deviation (SD higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97 was similar to that expected (0.96, 0.93-0.98 based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90 and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29 per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies

B-type natriuretic peptide: a novel early blood marker of acute myocardial infarction in patients with chest pain and no ST-segment elevation.

Science.gov (United States)

Bassan, Roberto; Potsch, Alfredo; Maisel, Alan; Tura, Bernardo; Villacorta, Humberto; Nogueira, Mônica Viegas; Campos, Augusta; Gamarski, Roberto; Masetto, Antonio Cláudio; Moutinho, Marco Aurélio

2005-02-01

This study was undertaken to determine the diagnostic value of admission B-type natriuretic peptide (BNP) for acute myocardial infarction (AMI) in patients with acute chest pain and no ST-segment elevation. A prospective study with 631 consecutive patients was conducted in the emergency department. Non-ST elevation AMI was present in 72 patients and their median admission BNP level was significantly higher than in unstable angina and non-acute coronary syndrome patients. Sensitivity of admission BNP for AMI (cut-off value of 100 pg/mL) was significantly higher than creatine kinase-MB (CKMB) and troponin-I on admission (70.8 vs. 45.8 vs. 50.7%, respectively, P<0.0001) and specificity was 68.9%. Simultaneous use of these markers significantly improved sensitivity to 87.3% and the negative predictive value to 97.3%. In multiple logistic regression analysis, admission BNP was a significant independent predictor of AMI, even when CKMB and troponin-I were present in the model. BNP is a useful adjunct to standard cardiac markers in patients presenting to the emergency department with chest pain and no ST-segment elevation, particularly if initial CKMB and/or troponin-I are non-diagnostic.

Natriuretic peptides stimulate the cardiac sodium pump via NPR-C-coupled NOS activation

DEFF Research Database (Denmark)

William, M.; Hamilton, E.J.; Garcia, A.

2008-01-01

Natriuretic peptides (NPs) and their receptors (NPRs) are expressed in the heart, but their effects on myocyte function are poorly understood. Because NPRs are coupled to synthesis of cGMP, an activator of the sarcolemmal Na(+)-K(+) pump, we examined whether atrial natriuretic peptide (ANP) regul...

Plant natriuretic peptides are apoplastic and paracrine stress response molecules

KAUST Repository

Wang, Yuhua

2011-04-07

Higher plants contain biologically active proteins that are recognized by antibodies against human atrial natriuretic peptide (ANP). We identified and isolated two Arabidopsis thaliana immunoreactive plant natriuretic peptide (PNP)-encoding genes, AtPNP-A and AtPNP-B, which are distantly related members of the expansin superfamily and have a role in the regulation of homeostasis in abiotic and biotic stresses, and have shown that AtPNP-A modulates the effects of ABA on stomata. Arabidopsis PNP (PNP-A) is mainly expressed in leaf mesophyll cells, and in protoplast assays we demonstrate that it is secreted using AtPNP-A:green fluorescent protein (GFP) reporter constructs and flow cytometry. Transient reporter assays provide evidence that AtPNP-A expression is enhanced by heat, osmotica and salt, and that AtPNP-A itself can enhance its own expression, thereby generating a response signature diagnostic for paracrine action and potentially also autocrine effects. Expression of native AtPNP-A is enhanced by osmotica and transiently by salt. Although AtPNP-A expression is induced by salt and osmotica, ABA does not significantly modulate AtPNP-A levels nor does recombinant AtPNP-A affect reporter expression of the ABA-responsive RD29A gene. Together, these results provide experimental evidence that AtPNP-A is stress responsive, secreted into the apoplastic space and can enhance its own expression. Furthermore, our findings support the idea that AtPNP-A, together with ABA, is an important component in complex plant stress responses and that, much like in animals, peptide signaling molecules can create diverse and modular signals essential for growth, development and defense under rapidly changing environmental conditions. © 2011 The Author.

Polymorphisms in the B-type natriuretic peptide (BNP) gene are associated with NT-proBNP levels but not with diabetic nephropathy or mortality in type 1 diabetic patients

DEFF Research Database (Denmark)

Lajer, Maria Stenkil; Tarnow, Lise; Jorsal, Anders

2007-01-01

BACKGROUND: Circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with diabetic nephropathy and independently predict excess cardiovascular morbidity and mortality. Therefore, we investigated the association between two polymorphisms -381T/C and 1551G....../A of the BNP gene, plasma NT-proBNP levels and mortality prognosis in 380 type 1 diabetic patients with and without diabetic nephropathy. METHODS: In a prospective observational follow-up study, 197 type 1 diabetic patients with diabetic nephropathy {121 men, age [mean (SD)] 41 +/- 9.5 years, duration...... of diabetes 28 +/- 8.0 years, glomerular filtration rate 67 +/- 28 ml/min/1.73 m2}, and a matched control group of 183 patients with longstanding type 1 diabetes and persistent normoalbuminuria (111 men, age 43 +/- 10.0 years, duration of diabetes 27 +/- 8.3 years) were followed for 12.6 (0.0-12.9) years...

The additive value of N-terminal pro-B-type natriuretic peptide testing at the emergency department in patients with acute dyspnoea.

Science.gov (United States)

van der Burg-de Graauw, N; Cobbaert, C M; Middelhoff, C J F M; Bantje, T A; van Guldener, C

2009-05-01

B-type natriuretic peptide (BNP) and its inactive counterpart NT-proBNP can help to identify or rule out heart failure in patients presenting with acute dyspnoea. It is not well known whether measurement of these peptides can be omitted in certain patient groups. We conducted a prospective observational study of 221 patients presenting with acute dyspnoea at the emergency department. The attending physicians estimated the probability of heart failure by clinical judgement. NT-proBNP was measured, but not reported. An independent panel made a final diagnosis of all available data including NT-proBNP level and judged whether and how NT-proBNP would have altered patient management. NT-proBNP levels were highest in patients with heart failure, alone or in combination with pulmonary failure. Additive value of NT-proBNP was present in 40 of 221 (18%) of the patients, and it mostly indicated that a more intensive treatment for heart failure would have been needed. Clinical judgement was an independent predictor of additive value of NT-proBNP with a maximum at a clinical probability of heart failure of 36%. NT-proBNP measurement has additive value in a substantial number of patients presenting with acute dyspnoea, but can possibly be omitted in patients with a clinical probability of heart failure of >70%.

B-Type Natriuretic Peptide Deletion Leads to Progressive Hypertension, Associated Organ Damage, and Reduced Survival: Novel Model for Human Hypertension.

Science.gov (United States)

Holditch, Sara J; Schreiber, Claire A; Nini, Ryan; Tonne, Jason M; Peng, Kah-Whye; Geurts, Aron; Jacob, Howard J; Burnett, John C; Cataliotti, Alessandro; Ikeda, Yasuhiro

2015-07-01

Altered myocardial structure and function, secondary to chronically elevated blood pressure, are leading causes of heart failure and death. B-type natriuretic peptide (BNP), a guanylyl cyclase A agonist, is a cardiac hormone integral to cardiovascular regulation. Studies have demonstrated a causal relationship between reduced production or impaired BNP release and the development of human hypertension. However, the consequences of BNP insufficiency on blood pressure and hypertension-associated complications remain poorly understood. Therefore, the goal of this study was to create and characterize a novel model of BNP deficiency to investigate the effects of BNP absence on cardiac and renal structure, function, and survival. Genetic BNP deletion was generated in Dahl salt-sensitive rats. Compared with age-matched controls, BNP knockout rats demonstrated adult-onset hypertension. Increased left ventricular mass with hypertrophy and substantially augmented hypertrophy signaling pathway genes, developed in young adult knockout rats, which preceded hypertension. Prolonged hypertension led to increased cardiac stiffness, cardiac fibrosis, and thrombi formation. Significant elongation of the QT interval was detected at 9 months in knockout rats. Progressive nephropathy was also noted with proteinuria, fibrosis, and glomerular alterations in BNP knockout rats. End-organ damage contributed to a significant decline in overall survival. Systemic BNP overexpression reversed the phenotype of genetic BNP deletion. Our results demonstrate the critical role of BNP defect in the development of systemic hypertension and associated end-organ damage in adulthood. © 2015 American Heart Association, Inc.

cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland

NARCIS (Netherlands)

H.R. de Jonge (Hugo); B.C. Tilly (Bernard); B.M. Hogema (Boris); D.J. Pfau (Daniel); C.A. Kelley (Catherine); M.H. Kelley (Megan); A.M. Melita (August); M.T. Morris (Montana); M.S. Viola (Maria); J.N. Forrest Jr. (John)

2014-01-01

textabstractThe in vitro perfused rectal gland of the dogfish shark (Squalus acanthias) and filter-grown monolayers of primary cultures of shark rectal gland (SRG) epithelial cells were used to analyze the signal transduction pathway by which C-type natriuretic peptide (CNP) stimulates chloride

Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion

DEFF Research Database (Denmark)

Kousholt, Birgitte S.; Larsen, Jens Kjærgaard Rolighed; Bisgaard, Line Stattau

2012-01-01

Aim: The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia–reperfusion damage. Materials and methods: The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect...... in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (~15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared...... with controls (P=0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P=0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P=0.0015 and 0.0019), and were associated with improved RNA integrity...

Natriuretic peptide infusion reduces myocardial injury during acute ischemia/reperfusion

DEFF Research Database (Denmark)

Kousholt, Birgitte S.; Larsen, Jens Kjærgaard Rolighed; Bisgaard, Line Stattau

2012-01-01

Aim: The aim of this study was to determine whether a natriuretic peptide infusion during reperfusion can reduce cardiomyocyte ischemia–reperfusion damage. Materials and methods: The effect of B-type natriuretic peptide (BNP) activity was assessed in vitro and in vivo: the cellular effect...... in apoptotic changes in the BNP-stimulated cells. Pigs tolerated the BNP and CD-NP (a CNP analogue) infusion well, with a decrease in systemic blood pressure (∼15 mmHg) and increased diuresis compared with the controls. Left ventricular pressure decreased in the pigs that received BNP infusion compared...... with controls (P=0.02). A similar trend was observed in the pigs that received CD-NP infusion, although this was not significant (P=0.3). BNP and CD-NP infusion in pigs reduced total cardiac troponin T release by 46 and 40%, respectively (P=0.0015 and 0.0019), and were associated with improved RNA integrity...

Amino-Terminal proB-Type Natriuretic Peptide Levels in the Umbilical Cord Blood of Neonates Differ According to the Type of Prenatally Diagnosed Congenital Heart Disease.

Science.gov (United States)

Bae, Jin Young; Cha, Hyun-Hwa; Seong, Won Joon

2015-12-01

The aim of this study was to investigate differences in amino-terminal proB-type natriuretic peptide (NT-proBNP) levels in the cord blood of neonates according to the type of congenital heart disease (CHD) and to evaluate the usefulness of NT-proBNP as a prognostic marker. We included 76 neonates with prenatally diagnosed CHD and 45 controls without CHD. Neonates were classified into five groups based on echocardiographic findings. The levels of NT-proBNP in the cord blood were examined and analyzed according to the neonatal outcomes. The levels of NT-proBNP were significantly elevated in the cord blood of neonates with CHD compared with that in the cord blood of controls. The levels of NT-proBNP in the group with right ventricular outflow tract obstruction without a ventricular septal defect were significantly increased compared to that in the other groups. The neonates that required acute surgical correction had higher levels of NT-proBNP in the cord blood, though they were not statistically significant. Meanwhile, NT-proBNP levels in the cord blood of neonates with functional single ventricle were significantly higher than that in the cord blood of those with functional biventricles. Significant differences in the levels of NT-proBNP between survivors and nonsurvivors were observed within 1 year of birth. In this study, we found that the levels of NT-proBNP in the cord blood of neonates with CHD were higher than the levels in controls. This finding was striking in the group with right ventricular outflow tract obstruction, and it was associated with surgery for functional single ventricle and 1-year survival.

Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

DEFF Research Database (Denmark)

Dimitrijevic, Ivan; Edvinsson, Lars; Chen, Qingwen

2009-01-01

expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. METHODS: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina...... pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ETA) and type B (ETB), and angiotensin type 1 (AT1) and type 2 (AT2) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro...

Prognostic value of B-type natriuretic peptide in elderly patients with aortic valve stenosis: the COFRASA-GENERAC study.

Science.gov (United States)

Cimadevilla, Claire; Cueff, Caroline; Hekimian, Guillaume; Dehoux, Monique; Lepage, Laurent; Iung, Bernard; Duval, Xavier; Huart, Virginie; Tubach, Florence; Vahanian, Alec; Messika-Zeitoun, David

2013-04-01

Previous studies suggested an independent prognostic value of B-type natriuretic peptide (BNP) in aortic valve stenosis (AS) but were impeded by small sample sizes and inclusion of relatively selected young patients. We aimed to evaluate the relationship among N-terminal fragment of proBNP (Nt-proBNP), AS severity, symptoms and outcome in a large cohort of elderly patients with AS. Observational cohort study, COhorte Française de Retrecissement Aortique du Sujet Agé (clinicalTrial.gov number-NCT00338676) and GENEtique du Retrecissement Aortique (clinicalTrial.gov number-NCT00647088). Single-centre study. Patients older than 70 years with at least mild AS. None. A comprehensive clinical, biological and echocardiographic evaluation was performed at study entry. Asymptomatic patients were prospectively followed on a 6-months basis and AS-related events (sudden death, congestive heart failure or new onset of AS-related symptoms) collected. We prospectively enrolled 361 patients (79±6 years, 230 severe AS). Nt-proBNP increased with the grade of AS severity and the NYHA class (all pvalue of Nt-proBNP for the diagnosis of severe symptomatic AS was only modest (area under the curve of the receiver operator characteristic analysis=0.73). At 2 years, 28 AS-related events occurred among 142 asymptomatic patients prospectively followed. Nt-proBNP was associated with outcome in univariate analysis (p=0.04) but not after adjustment for age, gender and AS severity (p=0.40). The present study clearly highlights the limitations of Nt-proBNP for the evaluation and management of AS patients. Our results suggest that Nt-proBNP should be considered cautiously, at least as a single criterion, in the decision-making process of AS patients especially in the elderly population.

Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA,partial cds and 3' UTR.

OpenAIRE

Landi, Stefano; Melaiu, Ombretta; Cabiati, Manuela; Landi, Debora; Caselli, Chiara; Prescimone, Tommaso; Giannessi, Daniela; Gemignani, Federica; Del Ry, Silvia

2010-01-01

LOCUS HQ419060 318 bp mRNA linear PRI 24-NOV-2010 DEFINITION Homo sapiens natriuretic peptide precursor type C (NPPC) mRNA, partial cds and 3' UTR. ACCESSION HQ419060 VERSION HQ419060.1 GI:312261407 KEYWORDS . SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 318) AUTHORS Landi,S., Melaiu,O., Cabiati,M., Landi,D., C...

Prognostic value of N-terminal pro-B-type natriuretic peptide in patients with acute coronary syndromes undergoing left main percutaneous coronary intervention.

Science.gov (United States)

Jaberg, Laurenz; Toggweiler, Stefan; Puck, Marietta; Frank, Michelle; Rufibach, Kaspar; Lüscher, Thomas F; Corti, Roberto

2011-01-01

Patients undergoing acute left main (LM) coronary artery revascularization have a high mortality and natriuretic peptides such as N-terminal pro-B-type (NT-proBNP) have been shown to have prognostic value in patients with acute coronary syndromes. The present study looked at the prognostic value of NT-proBNP in these patients. We studied all consecutive patients undergoing acute LM coronary artery percutaneous coronary intervention between January 2005 and December 2008 in whom NT-proBNP was measured (n=71). We analyzed the clinical characteristics and the short- and long-term outcomes in relation to NT-proBNP level at admission. Median NT-proBNP was 1,364 ng/L, ranging from 46 to 70,000 ng/L. NT-proBNP was elevated in 63 (89%) patients and was ≥1,000ng/L in 42 (59%). Log NT-proBNP (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.55-7.97, P=0.003) and left ventricular ejection fraction (HR 0.95, 95%CI 0.91-0.99, P=0.007) were predictors for all-cause mortality. Log NT-proBNP was the only independent significant predictor of cardiovascular mortality. In-hospital mortality was 0% for patients with NT-proBNP value for NT-proBNP in patients undergoing acute LM coronary artery intervention.

Model-based cost-effectiveness analysis of B-type natriuretic peptide-guided care in patients with heart failure.

Science.gov (United States)

Mohiuddin, Syed; Reeves, Barnaby; Pufulete, Maria; Maishman, Rachel; Dayer, Mark; Macleod, John; McDonagh, Theresa; Purdy, Sarah; Rogers, Chris; Hollingworth, William

2016-12-28

Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (-£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (-£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older patients with HFrEF, but more evidence is required, particularly with respect to the frequency, duration and BNP target for monitoring. Cost-effectiveness results from trials in specialist settings cannot be generalised to primary care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Vasoactive receptors in abdominal blood vessels of the dogfish shark, Squalus acanthias.

Science.gov (United States)

Evans, D H

2001-01-01

Previous studies have demonstrated that the ventral aorta of the dogfish shark, Squalus acanthias, responds to a variety of cell-signaling agents. To investigate the generality of vasoactive receptors in the shark vasculature, in particular a conductance artery (anterior mesenteric) and vein (posterior intestinal), I measured the effect of acetylcholine, endothelin, nitric oxide, natriuretic peptides, and prostaglandins on tension in isolated rings from these vessels. Both vessels responded to these agents, and responses to receptor-specific ligands for endothelin and natriuretic peptide receptors suggest that B-type endothelin receptors are expressed in both vessels and that the artery expresses both A- and B-type natriuretic peptide receptors; however, the vein (like the ventral aorta) expresses only the B-type natriuretic peptide receptor. My data suggest that a suite of signaling systems is ubiquitous in both arteries and veins in at least this elasmobranch species. Their role in hemodynamics and osmoregulation (perfusion of gill and rectal gland) remains to be determined.

Expression of a type B RIFIN in Plasmodium falciparum merozoites and gametes

DEFF Research Database (Denmark)

Mwakalinga, Steven B; Wang, Christian W; Bengtsson, Dominique C

2012-01-01

ABSTRACT: BACKGROUND: The ability of Plasmodium falciparum to undergo antigenic variation, by switching expression among protein variants encoded by multigene families, such as var, rif and stevor, is key to the survival of this parasite in the human host. The RIFIN protein family can be divided...... into A and B types based on the presence or absence of a 25 amino acid motif in the semi-conserved domain. A particular type B RIFIN, PF13_0006, has previously been shown to be strongly transcribed in the asexual and sexual stages of P. falciparum in vitro. METHODS: Antibodies to recombinant PF13_0006 RIFIN...... were used in immunofluorescence and confocal imaging of 3D7 parasites throughout the asexual reproduction and sexual development to examine the expression of PF13_0006. Furthermore, reactivity to recombinant PF13_0006 was measured in plasma samples collected from individuals from both East and West...

Time-dependent changes in B-type natriuretic peptide after heart transplantation: correlation with allograft rejection and function.

Science.gov (United States)

Bader, Feras M; Rogers, R Kevin; Kfoury, Abdallah G; Gilbert, Edward M; Horne, Ben D; Stehlik, Josef; Renlund, Dale G

2009-01-01

Endomyocardial biopsy is the gold standard to diagnose cardiac allograft rejection, although a noninvasive modality such as brain natriuretic peptide (BNP) is attractive. The authors examined the correlation of BNP levels with rejection patterns and allograft function in cardiac allograft recipients followed up to 8 years. One hundred forty-four consecutive patients underwent endomyocardial biopsy, right heart catheterization, and blood sampling. BNP levels decreased during the first 6 months after transplant but then reached a plateau. Time-dependent correlations were made between BNP levels and allograft rejection, left ventricular ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, and serum creatinine. BNP levels were not different between patients with any rejection pattern and no rejection prior to or after 6 months following transplant. BNP levels did not correlate with ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, or creatinine in the first 6 months after transplant. Statistically significant correlations existed between BNP and these parameters after 6 months following transplant. In cardiac transplant recipients, BNP levels decrease in the first 6 months following transplant and then reach a plateau regardless of the presence, type, or severity of allograft rejection. BNP levels do predict allograft rejection but correlate with allograft function after 6 months following transplant.

Plant natriuretic peptides control of synthesis and systemic effects

KAUST Repository

Wang, Yuhua; Donaldson, Lara Elizabeth; Gehring, Christoph A; Irving, Helen R.

2011-01-01

Plant natriuretic peptides (PNPs) are signaling molecules that are secreted into the apoplast particularly under conditions of biotic and abiotic stress. At the local level, PNPs modulate their own expression via feed forward and feedback loops

Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism.

Science.gov (United States)

Wendt, Daniel J; Dvorak-Ewell, Melita; Bullens, Sherry; Lorget, Florence; Bell, Sean M; Peng, Jeff; Castillo, Sianna; Aoyagi-Scharber, Mika; O'Neill, Charles A; Krejci, Pavel; Wilcox, William R; Rimoin, David L; Bunting, Stuart

2015-04-01

Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Risk stratification in stable coronary artery disease is possible at cardiac troponin levels below conventional detection and is improved by use of N-terminal pro-B-type natriuretic peptide

DEFF Research Database (Denmark)

Lyngbæk, Stig; Winkel, Per; Gøtze, Jens P

2014-01-01

AIMS: Low prevalence of detectable cardiac troponin in healthy people and low-risk patients previously curtailed its use. With a new high-sensitive cardiac troponin assay (hs-cTnT), concentrations below conventional detection may have prognostic value, notably in combination with N-terminal pro......-B-type natriuretic peptide (NT-pro-BNP). METHODS AND RESULTS: Biomarker concentrations were determined from serum obtained at enrolment in the CLARICOR trial involving 4197 patients with stable coronary artery disease (CAD) followed for 2.6 years. Serum hs-cTnT was detectable (above 3 ng/l) in 78% and above...... the conventional 99th percentile (13.5 ng/l) in 23%. Across all levels of hs-cTnT there was a graded increase in the risk of cardiovascular death after adjustment for known prognostic indicators: hazard ratio (HR) per unit increase in the natural logarithm of the hs-cTnT level, 1.49; 95% confidence interval (CI...

A glycosylated form of the human cardiac hormone pro B-type natriuretic peptide is an intrinsically unstructured monomeric protein.

Science.gov (United States)

Crimmins, Dan L; Kao, Jeffrey L-F

2008-07-01

The N-terminal fragment of pro B-type natriuretic peptide (NT-proBNP) and proBNP are used as gold standard clinical markers of myocardial dysfunction such as cardiac hypertrophy and left ventricle heart failure. The actual circulating molecular forms of these peptides have been the subject of intense investigation particularly since these analytes are measured in clinical assays. Conflicting data has been reported and no firm consensus on the exact nature of the molecular species exists. Because these clinical assays are immunoassay-based, specific epitopes are detected. It is conceivable then that certain epitopes may be masked and therefore unavailable for antibody binding, thus the importance of determining the nature of the circulating molecular forms of these analytes. This situation is an unavoidable Achilles' heel of immunoassays in general. A recombinant O-linked glycosylated form of proBNP has been show to mimic some of the properties of extracted plasma from a heart failure patient. In particular the recombinant and native material co-migrated as diffuse Western-immunostained bands on SDS-PAGE and each band collapsed to an apparent homogeneous band following deglycosylation. Thus, glycosylated-proBNP may be one such circulating form. Here we provide extensive physiochemical characterization for this O-linked protein and compare these results to other described circulating species, non-glycosylated-proBNP and NT-proBNP. It will be shown that glycosylation has no influence on the secondary and quaternary structure of proBNP. In fact, at moderate concentration in benign physiological neutral pH buffer, all three likely circulating species are essentially devoid of major secondary structure, i.e., are intrinsically unstructured proteins (IUPs). Furthermore, all three proteins exist as monomers in solution. These results may have important implications in the design of NT-proBNP/BNP immunoassays.

Associations between N-terminal pro-B-type natriuretic peptide and cardiac function in adults with corrected tetralogy of Fallot.

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Eindhoven, Jannet A; Menting, Myrthe E; van den Bosch, Annemien E; Cuypers, Judith A A E; Ruys, Titia P E; Witsenburg, Maarten; McGhie, Jackie S; Boersma, Eric; Roos-Hesselink, Jolien W

2014-07-01

Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with echocardiography and exercise capacity. NT-proBNP measurement, electrocardiography and detailed 2D-echocardiography were performed on the same day in 177 consecutive adults with ToF (mean age 34.6 ± 11.8 years, 58% male, 89% NYHA I, 29.3 ± 8.5 years after surgical correction). Thirty-eight percent of the patients also underwent a cardiopulmonary-exercise test. Median NT-proBNP was 16 [IQR 6.7-33.6] pmol/L, and was elevated in 55%. NT-proBNP correlated with right ventricular (RV) dilatation (r = 0.271, p present in 69 patients (39%). Moderate or severe pulmonary regurgitation was not associated with higher NT-proBNP. Tricuspid and pulmonary regurgitation peak velocities correlated with NT-proBNP (r = 0.305, p < 0.001 and r = 0.186, p = 0.045, respectively). LV twist was measured with speckle-tracking echocardiography in 71 patients. An abnormal LV twist (20 patients, 28%) was associated with elevated NT-proBNP (p = 0.030). No relationship between NT-proBNP and exercise capacity was found. NT-proBNP levels are elevated in more than 50% of adults with corrected ToF, while they are in stable clinical condition. Higher NT-proBNP is most strongly associated with elevated pulmonary pressures, and with LV dysfunction rather than RV dysfunction. NT-proBNP has the potential to become routine examination in patients with ToF to monitor ventricular function and may be used for timely detection of clinical deterioration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Relation of N-terminal pro B-type natriuretic peptide levels after symptom-limited exercise to baseline and ischemia levels.

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van der Zee, P Marc; Verberne, Hein J; van Spijker, Rianne C; van Straalen, Jan P; Fischer, Johan C; Sturk, Augueste; van Eck-Smit, Berthe L F; de Winter, Robbert J

2009-03-01

Circulating levels of B-type natriuretic peptide (BNP) and the amino-terminal portion of the prohormone (NT-proBNP) have been reported to increase immediately after myocardial ischemia. The association between extent of exercise-induced myocardial ischemia measured using myocardial perfusion scintigraphy and the magnitude and time course of changes in NT-proBNP was studied. One hundred one patients underwent symptom-limited exercise myocardial perfusion scintigraphy. Myocardial ischemia was assessed semiquantitatively. Serum samples were obtained before the start of exercise (baseline), at maximal exercise, and every hour up to 6 hours after maximal exercise. Myocardial ischemia was present in 37 patients (37%). NT-proBNP rapidly increased during exercise (to 113%, interquartile range 104 to 144, and 118%, interquartile range 106 to 142, of baseline, respectively), with a second peak at 4 (141%, interquartile range 119 to 169) and 5 hours (136%, interquartile range 93 to 188), respectively. Absolute changes between NT-proBNP at baseline and at maximum exercise in patients with versus without ischemia were similar (median, 30 pg/ml, interquartile range 7 to 45 vs 15, interquartile range 4 to 46, respectively, p = 0.230), but absolute change between baseline and the secondary peak was higher in patients with ischemia than in patients without ischemia (median 64 pg/ml, interquartile range 32 to 172 vs 34, interquartile range 19 to 85, respectively, p = 0.024). In multivariate linear stepwise regression analysis of determinants of changes in NT-proBNP after exercise, baseline NT-proBNP was the only independent determinant of absolute changes at maximum exercise, whereas the presence of ischemia was not predictive. Baseline NT-proBNP, cystatin C, and end-systolic volume were independent determinants of the absolute increase to secondary peak levels. In conclusion, myocardial ischemia per se did not lead to additional increases in NT-proBNP within 6 hours after exercise.

Limitations of N-Terminal Pro-B-Type Natriuretic Peptide in the Diagnosis of Heart Disease among Cancer Patients Who Present with Cardiac or Pulmonary Symptoms.

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Wieshammer, Siegfried; Dreyhaupt, Jens; Müller, Dirk; Momm, Felix; Jakob, Andreas

2016-01-01

Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml. A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy. Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity. The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

Incremental value of B-type natriuretic peptide for detection and risk reclassification of obstructive coronary artery disease on computed tomography angiography.

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Kawabe, Masayuki; Sato, Akira; Hoshi, Tomoya; Endo, Masae; Yoshida, Ikuo; Aonuma, Kazutaka

2017-04-01

B-type natriuretic peptide (BNP) is well known to increase as a result of left ventricular systolic dysfunction and is a useful diagnostic marker for heart failure. The purpose of this study was to assess the incremental value of BNP for predicting obstructive coronary artery disease (CAD) on computed tomography angiography (CTA) in patients with suspected CAD. This was an observational analysis of patients with stable CAD undergoing CTA in our institution between April 2008 and June 2014. Consecutive 947 patients with suspected CAD who underwent 64-slice CTA were enrolled. Obstructive CAD was defined as more than 50% luminal narrowing. We divided the patients into 2 groups according to median BNP value (20.3pg/ml). Duke clinical score for obstructive CAD was calculated for each patient. Obstructive CAD was found in 273 (28.0%) patients. Median follow-up period was 37 months (interquartile range 21-55 months). Kaplan-Meier curves showed that BNP above median was significantly associated with major adverse cardiac events (p=0.001). In multivariable logistic analysis, patients with BNP above median were associated with the presence of obstructive CAD, as compared with BNP below median [odds ratio, 2.55; 95% confidence interval (CI), 1.79-3.63; pvalue of the Duke clinical score and BNP, the predictive value of the Duke clinical score [area under the curve (AUC), 0.714] could be increased by BNP (AUC 0.745 for the combined model; prisk score. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Atrial natriuretic peptide down-regulates LPS/ATP-mediated IL-1β release by inhibiting NF-kB, NLRP3 inflammasome and caspase-1 activation in THP-1 cells.

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Mezzasoma, Letizia; Antognelli, Cinzia; Talesa, Vincenzo Nicola

2016-02-01

Atrial natriuretic peptide (ANP) is an hormone/paracrine/autocrine factor regulating cardiovascular homeostasis by guanylyl cyclase natriuretic peptide receptor (NPR-1). ANP plays an important role also in regulating inflammatory and immune systems by altering macrophages functions and cytokines secretion. Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine involved in a wide range of biological responses, including the immunological one. Unlike other cytokines, IL-1β production is rigorously controlled. Primarily, NF-kB activation is required to produce pro-IL-1β; subsequently, NALP3 inflammasome/caspase-1 activation is required to cleave pro-IL-1β into the active secreted protein. NALP3 is a molecular platform capable of sensing a large variety of signals and a major player in innate immune defense. Due to their pleiotropism, IL-1β and NALP3 dysregulation is a common feature of a wide range of diseases. Therefore, identifying molecules regulating IL-1β/NALP3/caspase-1 expression is an important step in the development of new potential therapeutic agents. The aim of our study was to evaluate the effect of ANP on IL-1β/NALP3/caspase-1 expression in LPS/ATP-stimulated human THP1 monocytes. We provided new evidence of the direct involvement of ANP/NPR-1/cGMP axis on NF-kB/NALP3/caspase-1-mediated IL-1β release and NF-kB-mediated pro-IL-1β production. In particular, ANP inhibited both NF-kB and NALP3/caspase-1 activation leading to pro- and mature IL-1β down-regulation. Our data, pointing out a modulatory role of this endogenous peptide on IL-1β release and on NF-kB/NALP3/caspase-1 activation, indicate an important anti-inflammatory and immunomodulatory effect of ANP via these mechanisms. We suggest a possible employment of ANP for the treatment of inflammatory/immune-related diseases and IL-1β/NALP3-associated disorders, affecting millions of people worldwide.

Usefulness of repeated N-terminal pro-B-type natriuretic peptide measurements as incremental predictor for long-term cardiovascular outcome after vascular surgery.

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Goei, Dustin; van Kuijk, Jan-Peter; Flu, Willem-Jan; Hoeks, Sanne E; Chonchol, Michel; Verhagen, Hence J M; Bax, Jeroen J; Poldermans, Don

2011-02-15

Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels improve preoperative cardiac risk stratification in vascular surgery patients. However, single preoperative measurements of NT-pro-BNP cannot take into account the hemodynamic stress caused by anesthesia and surgery. Therefore, the aim of the present study was to assess the incremental predictive value of changes in NT-pro-BNP during the perioperative period for long-term cardiac mortality. Detailed cardiac histories, rest left ventricular echocardiography, and NT-pro-BNP levels were obtained in 144 patients before vascular surgery and before discharge. The study end point was the occurrence of cardiovascular death during a median follow-up period of 13 months (interquartile range 5 to 20). Preoperatively, the median NT-pro-BNP level in the study population was 314 pg/ml (interquartile range 136 to 1,351), which increased to a median level of 1,505 pg/ml (interquartile range 404 to 6,453) before discharge. During the follow-up period, 29 patients (20%) died, 27 (93%) from cardiovascular causes. The median difference in NT-pro-BNP in the survivors was 665 pg/ml, compared to 5,336 pg/ml in the patients who died (p = 0.01). Multivariate Cox regression analyses, adjusted for cardiac history and cardiovascular risk factors (age, angina pectoris, myocardial infarction, stroke, diabetes mellitus, renal dysfunction, body mass index, type of surgery and the left ventricular ejection fraction), demonstrated that the difference in NT-pro-BNP level between pre- and postoperative measurement was the strongest independent predictor of cardiac outcome (hazard ratio 3.06, 95% confidence interval 1.36 to 6.91). In conclusion, the change in NT-pro-BNP, indicated by repeated measurements before surgery and before discharge is the strongest predictor of cardiac outcomes in patients who undergo vascular surgery. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis

NARCIS (Netherlands)

Troughton, Richard W.; Frampton, Christopher M.; Brunner-La Rocca, Hans-Peter; Pfisterer, Matthias; Eurlings, Luc W. M.; Erntell, Hans; Persson, Hans; O'Connor, Christopher M.; Moertl, Deddo; Karlström, Patric; Dahlström, Ulf; Gaggin, Hanna K.; Januzzi, James L.; Berger, Rudolf; Richards, A. Mark; Pinto, Yigal M.; Nicholls, M. Gary

2014-01-01

Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of

N-terminal pro-atrial natriuretic peptide measurement in plasma suggests covalent modification

DEFF Research Database (Denmark)

Hunter, Ingrid; Alehagen, Urban; Dahlström, Ulf

2011-01-01

different proANP assays on clinical outcome. METHODS: We examined 474 elderly patients with symptoms of heart failure presenting in a primary healthcare setting. Samples were analyzed with an automated immunoluminometric midregion proANP (MR-proANP) assay and a new processing-independent assay (PIA.......74 (95% CI, 0.66–0.81); P = 0.32]. The prognostic ability to report cardiovascular mortality during a 10-year follow-up revealed AUC values of 0.66 (95% CI, 0.60–0.71) for the proANP PIA and 0.69 (95% CI, 0.63–0.74) for the MR-proANP assay (P = 0.08, for comparing the 2 assays). CONCLUSIONS: Our data......BACKGROUND: The N-terminal fragment of cardiac-derived pro–B-type natriuretic peptide is a glycosylated polypeptide. It is unknown whether N-terminal pro–atrial natriuretic peptide (proANP) fragments are also covalently modified. We therefore evaluated the clinical performance of 2 distinctly...

N-terminal pro brain natriuretic peptide as a cardiac biomarker in Japanese hemodialysis patients.

Science.gov (United States)

Shimizu, Minako; Doi, Shigehiro; Nakashima, Ayumu; Naito, Takayuki; Masaki, Takao

2018-03-01

This study examined the clinical significance of N-terminal pro brain natriuretic peptide level as a cardiac marker in Japanese hemodialysis patients. This was a multicenter cross-sectional study involving 1428 Japanese hemodialysis patients. Ultrasonic cardiography data at post-hemodialysis were obtained from 395 patients. We examined whether serum N-terminal pro brain natriuretic peptide levels were associated with cardiac parameters and assessed cut-off values and investigated factors associated with a reduced ratio of N-terminal pro brain natriuretic peptide levels pre- and post-hemodialysis. Multivariate logistic regression analysis showed that pre- and post-hemodialysis N-terminal pro brain natriuretic peptide levels were associated with left ventricular hypertrophy on electrocardiogram (odds ratio: 3.10; p N-terminal pro brain natriuretic peptide levels were also significantly associated with ejection fraction on urine chorionic gonadotrophin (ultrasonic cardiography; odds ratio: 35.83; p N-terminal pro brain natriuretic peptide reduction ratio during a hemodialysis session correlated with Kt/V, membrane area, membrane type, modality, body weight gain ratio, treatment time, and ultrafiltration rate with multiple linear regression ( R: 0.53; p N-terminal pro brain natriuretic peptide are associated with the presence of left ventricular hypertrophy in this population. The post-hemodialysis N-terminal pro brain natriuretic peptide level is a useful marker for systolic dysfunction.

B-type natriuretic peptide is a determinant of the nocturnal increase in blood pressure independently of arterial hypertrophy and hypoxia.

Science.gov (United States)

Tabara, Yasuharu; Igase, Michiya; Miki, Tetsuro; Ohyagi, Yasumasa; Matsuda, Fumihiko; Kohara, Katsuhiko

2016-12-01

Loss of the nocturnal blood pressure (BP) drop is a risk factor for cardiovascular outcomes. However, clinical parameters that predispose to changes in nocturnal BP are currently uncertain. Given the possible involvement of salt sensitivity in nocturnal BP levels, we investigated a hypothesized association between plasma B-type natriuretic peptide (BNP) levels - a marker of body fluid retention - and nocturnal BP in a general population. Study participants were 1020 general individuals. Participants were divided into four groups (riser, nondipper, dipper, and extreme dipper) by their percentage changes in nocturnal SBP measured using an ambulatory BP monitor. Plasma BNP levels were positively associated with circadian BP change (β = 0.162, P < 0.001) independently of carotid hypertrophy (β = 0.133, P < 0.001), and awake heart rate (β = -0.102, P = 0.001) and SBP (β = -0.246, P < 0.001). Risers showed 1.6 times higher BNP levels than dippers, whereas oxygen desaturation during sleep was frequently observed in nondippers. Results of multinomial logistic regression analysis indicated that BNP level was a significant determinant for the riser pattern [odds ratio (OR) 1.27 (BNP 10 pg/ml), P < 0.001], whereas oxygen desaturation was specifically associated with the nondipping pattern (OR 1.04, P = 0.001). When participants were subdivided by BNP level, risers were more frequent in the high BNP subgroup (19.5%) than in the low BNP subgroup (6.7%) (OR 3.39, P < 0.001). A slight increase in plasma BNP level was independently associated with rising nocturnal BP. Our results may help to understand the pathophysiology of circadian BP variation, and be a clue to identify individuals who require careful BP monitoring.

Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials.

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Gianluigi Savarese

Full Text Available BACKGROUND: The role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF. METHODOLOGY/PRINCIPAL FINDINGS: MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005 and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000, but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077. When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007 and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003, but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438, whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371, HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142 or all-cause hospitalization (OR:0.726; CI:0.509 to 1.035; p = 0.077. [corrected]. CONCLUSIONS/SIGNIFICANCE: Use of cardiac peptides to guide

Manifold implications of obesity in ischemic heart disease among Japanese patients according to covariance structure analysis: Low reactivity of B-type natriuretic peptide as an intervening risk factor.

Science.gov (United States)

Tsutsumi, Joshi; Minai, Kosuke; Kawai, Makoto; Ogawa, Kazuo; Inoue, Yasunori; Morimoto, Satoshi; Tanaka, Toshikazu; Nagoshi, Tomohisa; Ogawa, Takayuki; Yoshimura, Michihiro

2017-01-01

Obesity is believed to be one of the major risk factors for cardiovascular disease in Western countries. However, the effects of obesity should be continuously examined in the Japanese population because the average bodily habitus differs among countries. In this study, we collectively examined the significance of obesity and obesity-triggered risk factors including the low reactivity of B-type natriuretic peptide (BNP), for ischemic heart disease (IHD) in Japanese patients. The study patients consisted of 1252 subjects (IHD: n = 970; non-IHD: n = 282). Multiple logistic regression analysis revealed that dyslipidemia, hypertension, diabetes, and the low reactivity of BNP were significant risk factors for IHD, but body mass index (BMI) was not. A theoretical path model was proposed by positioning BMI at the top of the hierarchical model. Exploratory factor analysis revealed that BMI did not play a causative role in IHD (P = NS). BMI was causatively linked to other risk factors (Pobesity per se is not a strong risk factor for IHD in Japanese patients. However, several important risk factors triggered by obesity exhibited a causative role for IHD. The low reactivity of BNP is a substantial risk factor for IHD.

Association between N-terminal proB-type Natriuretic Peptide and Depressive Symptoms in Patients with Acute Myocardial Infarction

Institute of Scientific and Technical Information of China (English)

Yan Ren; Jiao Jia; Jian Sa; Li-Xia Qiu; Yue-Hua Cui; Yue-An Zhang; Hong Yang

2017-01-01

Background:While depression and certain cardiac biomarkers are associated with acute myocardial infarction (AMI),the relationship between them remains largely unexplored.We examined the association between depressive symptoms and biomarkers in patients with AMI.Methods:We performed a cross-sectional study using data from 103 patients with AMI between March 2013 and September 2014.The levels of depression,N-terminal proB-type natriuretic peptide (NT-proBNP),and troponin I (TnI) were measured at baseline.The patients were divided into two groups:those with depressive symptoms and those without depressive symptoms according to Zung Self-rating Depression Scale (SDS) score.Baseline comparisons between two groups were made using Student's t-test for continuous variables,Chi-square or Fisher's exact test for categorical variables,and Wilcoxon test for variables in skewed distribution.Binomial logistic regression and multivariate linear regression were performed to assess the association between depressive symptoms and biomarkers while adjusting for demographic and clinical variables.Results:Patients with depressive symptoms had significantly higher NT-proBNP levels as compared to patients without depressive symptoms (1135.0 [131.5,2474.0] vs.384.0 [133.0,990.0],Z =-2.470,P =0.013).Depressive symptoms were associated with higher NT-proBNP levels (odds ratio [OR] =2.348,95％ CI:1.344 to 4.103,P =0.003) and higher body mass index (OR =1.169,95％ confidence interval [CI]:1.016 to 1.345,P =0.029).The total SDS score was associated with the NT-proBNP level (β =0.327,95％ CI:1.674 to 6.119,P =0.001) after multivariable adjustment.In particular,NT-proBNP was associated with three of the depressive dimensions,including core depression (β =0.299,95％ CI:0.551 to 2.428,P =0.002),cognitive depression (β =0.320,95％ CI:0.476 to 1.811,P=0.001),and somatic depression (β =0.333,95％ CI:0.240 to 0.847,P =0.001).Neither the overall depressive symptomatology nor the individual

Natriuretic Peptides in Kawasaki Disease: the Myocardial Perspective

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Nagib Dahdah

2013-01-01

Full Text Available Making a diagnosis of Kawasaki disease with certainty may be challenging, especially since the recognition of cases with incomplete diagnostic criteria and its consequences. In order to build the diagnostic case in daily practice, clinicians rely on clinical criteria established over four decades ago, aided by non specific laboratory tests, and above all inspired by experience. We have recently studied the diagnostic value of N-terminal pro B-type natriuretic peptide to improve the diagnostic certainty of cases with complete or incomplete clinical criteria. Our working hypothesis was based on the fact that myocarditis is present in nearly all Kawasaki disease patients supported by histology data. In this paper, we review these facts and the myocardial perspective from the diagnostic and the mechanistic standpoints.

Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

Science.gov (United States)

Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

2005-05-01

In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

Disposable amperometric magnetoimmunosensor for the sensitive detection of the cardiac biomarker amino-terminal pro-B-type natriuretic peptide in human serum

Energy Technology Data Exchange (ETDEWEB)

Esteban-Fernández de Ávila, Berta, E-mail: berta.efa@quim.ucm.es; Escamilla-Gómez, Vanessa, E-mail: vaneeg@quim.ucm.es; Campuzano, Susana, E-mail: susanacr@quim.ucm.es; Pedrero, María, E-mail: mpedrero@quim.ucm.es; Pingarrón, José M., E-mail: pingarro@quim.ucm.es

2013-06-19

Graphical abstract: -- Highlights: •Novel and sensitive amperometric magnetoimmunosensor for NT-proBNP detection. •Indirect competitive immunoassay onto HOOC-MBs and Au/SPEs as transducers. •Excellent analytical performance at levels clinically relevant in human serum. •Useful in clinical diagnosis and prognosis of cardiac diseases. -- Abstract: A novel amperometric magnetoimmunosensor using an indirect competitive format is developed for the sensitive detection of the amino-terminal pro-B-type natriuretic peptide (NT-proBNP). The immunosensor design involves the covalent immobilization of the antigen onto carboxylic-modified magnetic beads (HOOC-MBs) activated with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS), and further incubation in a mixture solution containing variable concentrations of the antigen and a fixed concentration of an HRP-labeled detection antibody. Accordingly, the target NT-proBNP in the sample and that immobilized on the MBs compete for binding to a fixed amount of the specific HRP-labeled secondary antibody. The immunoconjugate-bearing MBs are captured by a magnet placed under the surface of a disposable gold screen-printed electrode (Au/SPE). The amperometric responses measured at –0.10 V (vs. a Ag pseudo-reference electrode), upon addition of 3,3′,5,5′-tetramethylbenzidine (TMB) as electron transfer mediator and H{sub 2}O{sub 2} as the enzyme substrate, are used to monitor the affinity reaction. The developed magnetoimmunosensor provides attractive analytical characteristics in 10-times diluted human serum samples, exhibiting a linear range of clinical usefulness (0.12–42.9 ng mL{sup −1}) and a detection limit of 0.02 ng mL{sup −1}, which can be used in clinical diagnosis of chronic heart failure in the elderly and for classifying patients at risk of death after heart transplantation. The magnetoimmunosensor was successfully applied to the analysis of spiked human serum

Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

African Journals Online (AJOL)

AJB SERVER

2006-12-29

Dec 29, 2006 ... morphometry and function. Eliane Florencio ... granules is greatest in the right atrium followed by the left atrium and left auricle and right auricle, in this order. ... family: Atrial natriuretic peptide (ANP), Urodilatin, Brain natriuretic ...

Discordant expression of pro-B-type and pro-C-type natriuretic peptide in newborn infants of mothers with type 1 diabetes

DEFF Research Database (Denmark)

Nybo, Mads; Nielsen, Lars Bo; Nielsen, Søren Junge

2007-01-01

CNP-derived peptides in newborn infants. METHODS: Plasma concentrations of proCNP-derived peptides were measured in umbilical cord plasma and human placental tissue extracts using sequence-specific radioimmunoassays raised against N-terminal and C-terminal proCNP regions, respectively. RESULTS: The median pro...... in umbilical cord plasma compared to adult plasma (4.6 vs. 1.1), which parallels our earlier findings for proBNP and BNP peptides. CONCLUSIONS: There is a discordant expression of CNP and BNP peptides in newborn infants of mothers with diabetes. Moreover, fetal metabolism of proCNP and CNP appears to differ...

Expression of a type B RIFIN in Plasmodium falciparum merozoites and gametes

Directory of Open Access Journals (Sweden)

Mwakalinga Steven B

2012-12-01

Full Text Available Abstract Background The ability of Plasmodium falciparum to undergo antigenic variation, by switching expression among protein variants encoded by multigene families, such as var, rif and stevor, is key to the survival of this parasite in the human host. The RIFIN protein family can be divided into A and B types based on the presence or absence of a 25 amino acid motif in the semi-conserved domain. A particular type B RIFIN, PF13_0006, has previously been shown to be strongly transcribed in the asexual and sexual stages of P. falciparum in vitro. Methods Antibodies to recombinant PF13_0006 RIFIN were used in immunofluorescence and confocal imaging of 3D7 parasites throughout the asexual reproduction and sexual development to examine the expression of PF13_0006. Furthermore, reactivity to recombinant PF13_0006 was measured in plasma samples collected from individuals from both East and West African endemic areas. Results The PF13_0006 RIFIN variant appeared expressed by both released merozoites and gametes after emergence. 7.4% and 12.1% of individuals from East and West African endemic areas, respectively, carry plasma antibodies that recognize recombinant PF13_0006, where the antibody responses were more common among older children. Conclusions The stage specificity of PF13_0006 suggests that the diversity of RIFIN variants has evolved to provide multiple specialized functions in different stages of the parasite life cycle. These data also suggest that RIFIN variants antigenically similar to PF13_0006 occur in African parasite populations.

Effect of Pancreatic Hormones on pro-Atrial Natriuretic Peptide in Humans

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Zois, Nora E.; Terzic, Dijana; Faerch, Kristine

2017-01-01

Plasma concentrations of pro-Atrial natriuretic peptide, proANP, are decreased in obesity and diabetes. Decreased proANP concentrations have also been noted after meal intake, and recently, a glucose-mediated regulation of ANP gene expression was reported. Hence, we evaluated the effects of insul...

Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning

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Neinast, Michael D.; Frank, Aaron P.; Zechner, Juliet F.; Li, Quanlin; Vishvanath, Lavanya; Palmer, Biff F.; Aguirre, Vincent; Gupta, Rana K.; Clegg, Deborah J.

2015-01-01

Objective Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These ‘BRITE/beige’ adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as “browning.” Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions Upregulation of Nppb, Npr1, Npr2, and β3-adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive

Differential effects of doxorubicin on atrial natriuretic peptide expression in vivo and in vitro

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ASIM RAHMAN

2001-01-01

Full Text Available Doxorubicin (Dox is a potent anti-cancer agent with cardiotoxic side-effects but the mechanism of its cardiotoxicity and its effect on expression of the vasoactive atrial natriuretic peptide (ANP, an important marker for cardiac hypertrophy, are little understood. The present study examined Dox-induced changes in vivo in hearts of 6 mongrel dogs and 5 Sprague-Dawley rats and in vitro in cardiac cultures of neonatal rats. Quantitative RT-PCR analysis using g32-p labeled primers for ß-actin, phospholamban (PLB and ANP showed a selective 5-fold increase of ANP mRNA in Dox-treated dog hearts in comparison to controls. Similarly, northern analysis of GAPD, ß-actin, cardiac a-actin and ANP gave a selective 4.5-fold increase in ANP transcripts in Dox-treated rat hearts. On the other hand, there was a selective decrease (approximately 39% of ANP transcripts in Dox-treated cardiac cultures relative to controls. Immunohistochemistry localized the ANP changes both in tissue sections and in cultures to the cardiomyocytes. The data clearly showed that Dox selectively increases ANP expression in dog and rat hearts in absence of cardiocyte hypertrophy but selectively decreases it in cardiac cultures. This differential effect of Dox on cardiocytes in vivo and in vitro should be a useful parameter for studies of transcriptional control of ANP expression.

Plasma B-type natriuretic peptide as a predictor of cardiovascular events in subjects with atrial fibrillation: a community-based study.

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Motoyuki Nakamura

Full Text Available OBJECTIVES: Atrial fibrillation (AF is a significant public health issue due to its high prevalence in the general population, and is associated with an increased risk of cardiovascular (CV events including systemic thrombo-embolism, heart failure, and coronary artery disease. The relationship between plasma B-type natriuretic peptide (BNP and CV risk in real world AF subjects remains unknown. METHODS: The subject of the study (n = 228; mean age = 69 years was unselected individuals with AF in a community-based population (n = 15,394; AF prevalence rate = 1.5%. The CV event free rate within each BNP tertile was estimated, and Cox regression analysis was performed to examine the relative risk of the onset of CV events among the tertiles. The prognostic ability of BNP was compared to an established risk score for embolic events (CHADS2 score. In addition, to determine the usefulness of BNP as a predictor in addition to CHADS2 score, we calculated Net Reclassification Improvement (NRI and Integrated Discrimination Improvement (IDI indices. RESULTS: During the follow-up period 58 subjects experienced CV events (52 per 1,000 person-years. The event-free ratio was significantly lower in the highest tertile (p < 0.02. After adjustment for established CV risk factors, the hazard ratio (HR of the highest tertile was significantly higher than that of the lowest tertile (HR = 2.38; p < 0.02. The predictive abilities of plasma BNP in terms of sensitivity and specificity for general CV events were comparable to those of CHADS2 score. Adding BNP to the CHADS2 score only model improved the NRI (0.319; p < 0.05 and the IDI (0.046; p < 0.05. CONCLUSION: Plasma BNP is a valuable biomarker both singly or in combination with an established scoring system for assessing general CV risk including stroke, heart failure and acute coronary syndrome in real-world AF subjects.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

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McNeal-Davidson, Ariane; Fournier, Anne; Spigelblatt, Linda; Saint-Cyr, Claire; Mir, Thomas S; Nir, Amiram; Dallaire, Frédéric; Cousineau, Jocelyne; Delvin, Edgard; Dahdah, Nagib

2012-10-01

The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

B-type Natriuretic Peptide and RISK-PCI Score in the Risk Assessment in Patients with STEMI Treated by Primary Percutaneous Coronary Intervention.

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Asanin, Milika; Mrdovic, Igor; Savic, Lidija; Matic, Dragan; Krljanac, Gordana; Vukcevic, Vladan; Orlic, Dejan; Stankovic, Goran; Marinkovic, Jelena; Stankovic, Sanja

2016-01-01

RISK-PCI score is a novel score for risk stratification of patients with ST elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). The aim of this study was to evaluate the role of B-type natriuretic peptide (BNP) and the RISK-PCI score for early risk assessment in patients with STEMI treated by pPCI. In 120 patients with STEMI treated by pPCI, BNP was measured on admission before pPCI. The primary end point was 30-day mortality. The ROC curve analysis revealed that the most powerful predictive factors of 30-day mortality were the plasma level of BNP ≥ 206.6 pg/mL with the sensitivity of 75% and specificity of 87.5% and the RISK-PCI score ≥ 5.25 with the sensitivity of 75% and specificity of 85.7%. Thirty-day mortality was 6.7%. After multivariate adjustment, admission BNP (≥ 206.6 pg/mL) (OR 2.952, 95% CI 1.072 - 8.133, p = 0.036) and the RISK-PCI score (≥ 5.25) (OR 2.284, 95% CI 1.140-4.578, p = 0.020) were independent predictors of 30-day mortality. The area under the ROC curve using the RISK-PCI score and BNP to detect mortality was 0.828 (p = 0.002) and 0.903 (p PCI score increased the area under the ROC to 0.949 (p PCI score for 30-day mortality. BNP on admission and the RISK-PCI score were the independent predictors of 30-day mortality in patients with the STEMI treated by pPCI. BNP in combination with the RISK-PCI score showed the way to more accurate risk assessment in patients with STEMI treated by pPCI.

Vascular relaxation induced by C-type natriuretic peptide involves the ca2+/NO-synthase/NO pathway.

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Fernanda A Andrade

Full Text Available AIMS: C-type natriuretic peptide (CNP and nitric oxide (NO are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3 contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery. MAIN METHODS: Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser1177 of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry. KEY FINDINGS: CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO0 scavenger. CNP did not change the phosphorylation of Ser1177, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca2+]c in endothelial cells and a decrease in [Ca2+]c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas. SIGNIFICANCE: These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca2+]c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP.

Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion.

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Bochra Tourki

Full Text Available Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2 is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP. Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR. We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial

Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study.

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Celik, Onder; Sahin, Ibrahim; Celik, Nilufer; Hascalik, Seyma; Keskin, Lezzan; Ozcan, Hamdi; Uckan, Ahmet; Kosar, Feridun

2007-11-01

In addition to the negative effect on fertility, polycystic ovary syndrome (PCOS) has been associated with cardiac pathology. Brain natriuretic peptide (BNP) is a possible marker for cardiac risk, therefore we investigated whether N-terminal pro-B-type BNP (NT-proBNP) increases in women with PCOS compared with healthy women of comparable age and body mass index. Thirty women with PCOS and 30 healthy women not suffering from overt cardiac disease were involved in the study. Fasting insulin and serum NT-proBNP levels were measured, and M-Mode echocardiography was performed. Insulin resistance was calculated using the homeostasis model assessment insulin resistance index (HOMA-IR). PCOS subjects had higher NT-proBNP levels than the control subjects (P PCOS subjects (but none of the controls), including valvular heart disease in nine, diastolic dysfunction in two, right ventricular enlargement in one, right atrial enlargement in one and pulmonary hypertension in one. PCOS subjects (n = 30) showed an increased left ventricular mass (LVM) (P PCOS subjects (n = 30). The present study demonstrated that the level of NT-proBNP was increased in PCOS subjects with asymptomatic heart disease.

The response of the natriuretic peptide system to water deprivation in the desert rodent, Notomys alexis.

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Heimeier, Rachel A; Donald, John A

2006-02-01

Natriuretic peptides (NPs) are regulatory molecules that cause cGMP-mediated diuresis and natriuresis in mammals. Accordingly, it is interesting to consider their role in desert-adapted animals in which water is often limited. This study investigated the response of the natriuretic peptide (NP) system to varying periods of water deprivation (WD) in the Australian desert rodent species, Notomys alexis. It was hypothesised that the expression of the NP system will be down-regulated in water-deprived N. alexis compared to water-replete animals. The plasma levels of ANP were significantly reduced after 3 days of WD, but were unaffected by 7, 14 and 28 days of WD. Water deprivation for 3, 7, 14 days had a variable effect on the mRNA expression of ANP, CNP, NPR-A, NPR-B, and NPR-C, and a uniform down-regulation was not observed. However, after 28 days of WD, mRNA expression was similar to water-replete animals, except for NPR-A. Surprisingly, 7 and 14 days of WD caused an up-regulation in the ability of ANP to stimulate cGMP; this also occurred at 14 days for CNP. Taken together, the mRNA expression and peptide mediated guanylyl cyclase activity data after WD were in the opposite direction to what was predicted. Interestingly, after 28 days of WD, most parameters were similar to those of water-replete animals, which indicates that a down-regulation of the NP system is not part of the physiological response to an absence of free water in N. alexis.

Regulation of hippocampal synaptic plasticity thresholds and changes in exploratory and learning behavior in dominant negative NPR-B mutant rats

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Gleb eBarmashenko

2014-12-01

Full Text Available The second messenger cyclic GMP affects synaptic transmission and modulates synaptic plasticity and certain types of learning and memory processes. The impact of the natriuretic peptide receptor B (NPR-B and its ligand C-type natriuretic peptide (CNP, one of several cGMP producing signalling systems, on hippocampal synaptic plasticity and learning is, however, less well understood. We have previously shown that the NPR-B ligand CNP increases the magnitude of long-term depression (LTD in hippocampal area CA1, while reducing the induction of long-term potentiation (LTP. We have extended this line of research to show that bidirectional plasticity is affected in the opposite way in rats expressing a dominant-negative mutant of NPR-B (NSE-NPR-BdeltaKC lacking the intracellular guanylyl cyclase domain under control of a promoter for neuron-specific enolase. The brain cells of these transgenic rats express functional dimers of the NPR-B receptor containing the dominant-negative NPR-BdeltaKC mutant, and therefore show decreased CNP-stimulated cGMP-production in brain membranes. The NPR-B transgenic rats display enhanced LTP but reduced LTD in hippocampal slices. When the frequency-dependence of synaptic modification to afferent stimulation in the range of 1-100 Hz was assessed in transgenic rats the threshold for LTP induction was raised, but LTD induction was facilitated. In parallel, NPR-BdeltaKC rats exhibited an enhancement in exploratory and learning behavior. These results indicate that bidirectional plasticity and learning and memory mechanism are affected in transgenic rats expressing a dominant-negative mutant of NPR-B. Our data substantiate the hypothesis that NPR-B-dependent cGMP signalling has a modulatory role for synaptic information storage and learning.

Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary.

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Pereira, Virginia M; Honorato-Sampaio, Kinulpe; Martins, Almir S; Reis, Fernando M; Reis, Adelina M

2014-10-01

Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries. Copyright © 2014 Elsevier Inc. All rights reserved.

Deletion of Protein Tyrosine Phosphatase 1B (PTP1B Enhances Endothelial Cyclooxygenase 2 Expression and Protects Mice from Type 1 Diabetes-Induced Endothelial Dysfunction.

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David J Herren

Full Text Available Protein tyrosine phosphatase 1B (PTP1B dephosphorylates receptors tyrosine kinase and acts as a molecular brake on insulin signaling pathway. Conditions of metabolic dysfunction increase PTP1B, when deletion of PTP1B protects against metabolic disorders by increasing insulin signaling. Although vascular insulin signaling contributes to the control of glucose disposal, little is known regarding the direct role of PTP1B in the control of endothelial function. We hypothesized that metabolic dysfunctions increase PTP1B expression in endothelial cells and that PTP1B deletion prevents endothelial dysfunction in situation of diminished insulin secretion. Type I diabetes (T1DM was induced in wild-type (WT and PTP1B-deficient mice (KO with streptozotocin (STZ injection. After 28 days of T1DM, KO mice exhibited a similar reduction in body weight and plasma insulin levels and a comparable increase in glycemia (WT: 384 ± 20 vs. Ko: 432 ± 29 mg/dL, cholesterol and triglycerides, as WT mice. T1DM increased PTP1B expression and impaired endothelial NO-dependent relaxation, in mouse aorta. PTP1B deletion did not affect baseline endothelial function, but preserved endothelium-dependent relaxation, in T1DM mice. NO synthase inhibition with L-NAME abolished endothelial relaxation in control and T1DM WT mice, whereas L-NAME and the cyclooxygenases inhibitor indomethacin were required to abolish endothelium relaxation in T1DM KO mice. PTP1B deletion increased COX-2 expression and PGI2 levels, in mouse aorta and plasma respectively, in T1DM mice. In parallel, simulation of diabetic conditions increased PTP1B expression and knockdown of PTP1B increased COX-2 but not COX-1 expression, in primary human aortic endothelial cells. Taken together these data indicate that deletion of PTP1B protected endothelial function by compensating the reduction in NO bioavailability by increasing COX-2-mediated release of the vasodilator prostanoid PGI2, in T1DM mice.

Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens.

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Lin, Shumao; Li, Hongmei; Mu, Heping; Luo, Wen; Li, Ying; Jia, Xinzheng; Wang, Sibing; Jia, Xiaolu; Nie, Qinghua; Li, Yugu; Zhang, Xiquan

2012-07-10

A deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week-old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition. At the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down-regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3' untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines. There is a critical miRNA, let-7b

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

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Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

2008-05-01

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p NT-proBNP (p NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

The interrelationship between preoperative anemia and N-terminal pro-B-type natriuretic peptide: the effect on predicting postoperative cardiac outcome in vascular surgery patients.

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Goei, Dustin; Flu, Willem-Jan; Hoeks, Sanne E; Galal, Wael; Dunkelgrun, Martin; Boersma, Eric; Kuijper, Ruud; van Kuijk, Jan-Peter; Winkel, Tamara A; Schouten, Olaf; Bax, Jeroen J; Poldermans, Don

2009-11-01

N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts adverse cardiac outcome in patients undergoing vascular surgery. However, several conditions might influence this prognostic value, including anemia. In this study, we evaluated whether anemia confounds the prognostic value of NT-proBNP for predicting cardiac events in patients undergoing vascular surgery. A detailed cardiac history, resting echocardiography, and hemoglobin and NT-proBNP levels were obtained in 666 patients before vascular surgery. Anemia was defined as serum hemoglobin value of NT-proBNP for the prediction of the composite end point. Multivariable regression analysis was used to assess the additional value of NT-proBNP for the prediction of postoperative cardiac events in nonanemic and anemic patients. Anemia was present in 206 patients (31%) before surgery. Hemoglobin level was inversely related with the NT-proBNP levels (beta coefficient = -2.242; P = 0.025). The optimal predictive cutoff value of NT-proBNP for predicting the composite cardiovascular outcome was 350 pg/mL. After adjustment for clinical cardiac risk factors, both anemia (odds ratio [OR] 1.53; 95% confidence interval [CI]: 1.07-2.99) and increased levels of NT-proBNP (OR 4.09; 95% CI: 2.19-7.64) remained independent predictors for postoperative cardiac events. However, increased levels of NT-proBNP were not predictive for the risk of adverse cardiac events in the subgroup of anemic patients (OR 2.16; 95% CI: 0.90-5.21). Both anemia and NT-proBNP are independently associated with an increased risk for postoperative cardiac events in patients undergoing vascular surgery. NT-proBNP has less predictive value in anemic patients.

Brain natriuretic peptide: Diagnostic potential in dogs

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Spasojević-Kosić Ljubica

2009-01-01

Full Text Available The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .

Comparative analysis of B7-1 and B7-2 expression in Langerhans cells: differential regulation by T helper type 1 and T helper type 2 cytokines.

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Kawamura, T; Furue, M

1995-07-01

Epidermal Langerhans cells (LC) are Ia-bearing potent antigen-presenting cells (APC) of dendritic cell lineage that play a crucial role in primary and secondary T cell-dependent immune responses. LC express several costimulatory molecules such as B7, which has been implicated as one of the important determinants of professional APC. Recently, B7 antigens have been shown to include three distinct molecules termed B7-1, B7-2, and B7-3, and the expression of B7-1 and B7-2 in LC has been already confirmed. However, little is known of the regulation of B7-1 and B7-2 expression in LC. We demonstrated that LC do not express B7-1 and B7-2 in situ; however, the expression of both molecules is rapidly induced during the first 3 days of culture, and high levels of expression are maintained at least until day 6. We show that the expression of B7-2 in LC is much higher than that of B7-1 in each experiment, and that B7-1 and B7-2 expression is reproducibly augmented by interleukin (IL)-4 in a dose-dependent manner; however, IL-2 affected expression very little. Finally, B7-1 expression is significantly and dose-dependently down-regulated by interferon (IFN)-gamma or IL-10, and B7-2 expression is consistently inhibited by IL-10, but not by IFN-gamma. The effects of these cytokines are active only in the induction phase (during first 3 days of culture) of B7 expression: the modulatory effects of cytokines are hardly detected in the plateau phase (days 4 to 6 of culture) of B7 expression in LC. These findings suggest that B7-1 and B7-2 expression are indeed selectively and differentially regulated by these T cell-derived cytokines, and that the cytokines may modulate the synthesis of B7 molecules rather than the degradation of already-expressed B7 molecules.

Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

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F.B. Silva

2015-02-01

Full Text Available The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF. Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23, a group that received chemotherapy + tamoxifen (n=21, and a group that received only tamoxifen (n=16. Plasma levels of NT-proBNP were assessed at 0 (T0, 6 (T6, and 12 (T12 months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Atrial natriuretic peptides in plasma

DEFF Research Database (Denmark)

Goetze, Jens Peter; Hansen, Lasse H; Terzic, Dijana

2014-01-01

Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

Atrial natriuretic peptides in plasma

DEFF Research Database (Denmark)

Goetze, Jens P; Holst Hansen, Lasse; Terzic, Dijana

2015-01-01

Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

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Heinisch, B B; Vila, G; Resl, M; Riedl, M; Dieplinger, B; Mueller, T; Luger, A; Pacini, G; Clodi, M

2012-05-01

B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m(2); fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured. Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. ClinicalTrials.gov: NCT01324739 The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

Predicting short-term mortality in advanced decompensated heart failure - role of the updated acute decompensated heart failure/N-terminal pro-B-type natriuretic Peptide risk score.

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Scrutinio, Domenico; Ammirati, Enrico; Passantino, Andrea; Guida, Pietro; D'Angelo, Luciana; Oliva, Fabrizio; Ciccone, Marco Matteo; Iacoviello, Massimo; Dentamaro, Ilaria; Santoro, Daniela; Lagioia, Rocco; Sarzi Braga, Simona; Guzzetti, Daniela; Frigerio, Maria

2015-01-01

The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF). We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow χ(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models. Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.

C-Type Natriuretic Peptide Analog as Therapy for Achondroplasia.

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Legeai-Mallet, Laurence

2016-01-01

Fibroblast growth factor receptor 3 (FGFR3) is an important regulator of bone formation. Gain-of-function mutations in the FGFR3 gene result in chondrodysplasias which include achondroplasia (ACH), the most common form of dwarfism, in which skull, appendicular and axial skeletons are affected. The skeletal phenotype of patients with ACH showed defective proliferation and differentiation of the chondrocytes in the growth plate cartilage. Both endochondral and membranous ossification processes are disrupted during development. At cellular level, Fgfr3 mutations induce increased phosphorylation of the tyrosine kinase receptor FGFR3, which correlate with an enhanced activation of its downstream signaling pathways. Potential therapeutic strategies have emerged for ACH. Several preclinical studies have been conducted such as the C-type natriuretic peptide (CNP) analog (BMN111), intermittent parathyroid hormone injections, soluble FGFR3 therapy, and meclozine and statin treatments. Among the putative targets to antagonize FGFR3 signaling, CNP (or BMN111) is one of the most promising strategies. BMN111 acts as a key regulator of longitudinal bone growth by downregulating the mitogen-activated protein kinase pathway, which is activated as a result of a FGFR3 gain-of-function mutation. Preclinical studies showed that BMN111 treatment led to a large improvement in skeletal parameters in Fgfr3Y367C/+ mice mimicking ACH. In 2014, a clinical trial (phase 2) of BMN111 in pediatric patients with ACH has started. This first clinical trial marks the first big step towards real treatment for these patients. © 2016 S. Karger AG, Basel.

Unraveling the Molecular Complexity of O-Glycosylated Endogenous (N-Terminal) pro-B-Type Natriuretic Peptide Forms in Blood Plasma of Patients with Severe Heart Failure.

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Halfinger, Bernhard; Hammerer-Lercher, Angelika; Amplatz, Benno; Sarg, Bettina; Kremser, Leopold; Lindner, Herbert H

2017-01-01

Currently, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its physiologically active counterpart, BNP, are most frequently used as biomarkers for diagnosis, prognosis, and disease monitoring of heart failure (HF). Commercial NT-proBNP and BNP immunoassays cross-react to varying degrees with unprocessed proBNP, which is also found in the circulation. ProBNP processing and immunoassay response are related to O-linked glycosylation of NT-proBNP and proBNP. There is a clear and urgent need to identify the glycosylation sites in the endogenously circulating peptides requested by the community to gain further insights into the different naturally occurring forms. The glycosylation sites of (NT-) proBNP (NT-proBNP and/or proBNP) were characterized in leftovers of heparinized plasma samples of severe HF patients (NT-proBNP: >10000 ng/L) by using tandem immunoaffinity purification, sequential exoglycosidase treatment for glycan trimming, β-elimination and Michael addition chemistry, as well as high-resolution nano-flow liquid chromatography electrospray multistage mass spectrometry. We describe 9 distinct glycosylation sites on circulating (NT-) proBNP in HF patients. Differentially glycosylated variants were detected based on highly accurate mass determination and multistage mass spectrometry. Remarkably, for each of the identified proteolytic glycopeptides, a nonglycosylated form also was detectable. Our results directly demonstrate for the first time a rather complex distribution of the endogenously circulating glycoforms by mass spectrometric analysis in HF patients, and show 9 glycosites in human (NT-) proBNP. This information may also have an impact on commercial immunoassays applying antibodies specific for the central region of (NT-) proBNP, which detect mostly nonglycosylated forms. © 2016 American Association for Clinical Chemistry.

The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation.

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Kawabata, Mihoko; Goya, Masahiko; Takagi, Takamitsu; Yamashita, Shu; Iwai, Shinsuke; Suzuki, Masahito; Takamiya, Tomomasa; Nakamura, Tomofumi; Hayashi, Tatsuya; Yagishita, Atsuhiko; Sasaki, Takeshi; Takahashi, Yoshihide; Ono, Yuhichi; Hachiya, Hitoshi; Yamauchi, Yasuteru; Otomo, Kenichiro; Nitta, Junichi; Okishige, Kaoru; Nishizaki, Mitsuhiro; Iesaka, Yoshito; Isobe, Mitsuaki; Hirao, Kenzo

2016-12-01

Atrial fibrillation (AF) often coexists with Wolff-Parkinson-White (WPW) syndrome. We compared the efficacy of Kent bundle ablation alone and additional AF ablation on accompanying AF, and examined which patients would still have a risk of AF after successful Kent bundle ablation. This retrospective multicenter study included 96 patients (56±15 years, 72 male) with WPW syndrome and AF undergoing Kent bundle ablation. Some patients underwent simultaneous pulmonary vein isolation (PVI) for AF. The incidence of post-procedural AF was examined. Sixty-four patients underwent only Kent bundle ablation (Kent-only group) and 32 also underwent PVI (+PVI group). There was no significant difference in the basic patient characteristics between the groups. Additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p=0.53). In the Kent-only group, AF episodes remained in 25.0% during the follow-up (709 days). A univariate analysis showed that age ≥60 years, left atrial dimension ≥38mm, B-type natriuretic peptide (BNP) ≥40pg/ml, and concomitant hypertension were predictive factors for residual AF. However, in the multivariate analysis, only BNP ≥40pg/ml remained as an independent predictive factor (HR=17.1 and CI: 2.3-128.2; p=0.006). Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact of preventing recurrence of AF in select patients. Screening the BNP level would help decide the strategy to manage those patients. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Pro B-type natriuretic peptide plasma value: a new criterion for the prediction of short- and long-term outcomes after transcatheter aortic valve implantation.

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López-Otero, Diego; Trillo-Nouche, Ramiro; Gude, Francisco; Cid-Álvarez, Belen; Ocaranza-Sanchez, Raimundo; Alvarez, Melisa Santas; Lear, Pamela V; Gonzalez-Juanatey, José R

2013-09-30

To determine the prognostic value of pro B-type natriuretic peptide (pro-BNP) to predict mortality after transcatheter aortic valve implantation (TAVI). Logistic EuroSCORE (LES) overestimates observed mortality after TAVI. A new risk score specific to TAVI is needed to accurately assess mortality and outcome. Eighty-five patients were included. Indications for TAVI were nonoperable or surgically high-risk patients (LES>20%). Pro-BNP was measured 24h before the procedure. Cox proportional hazards model was used to evaluate clinical factors. The predictive accuracy of these Cox models was determined by using time-dependent receiver operating characteristic (ROC) curves. Pro-BNP levels (log-transformed) were significantly higher in non-survivors than in survivors at 30 days (3.36 ± 0.43 vs. 3.81 ± 0.43, p<0.004) and at the end of follow-up (3.34 ± 0.42 vs. 3.63 ± 0.48, p<0.011). Multivariate analysis revealed that only increased log pro-BNP levels were associated with higher mortality rate at short [hazard ratio (HR) (95% confidence intervals (CI)]=5.35 (1.74-16.5), p=0.003] and long-term follow-ups [HR=11 (CI: 1.51-81.3), p=0.018]. LES was not associated with increased mortality at either time point [HR=1.03 (CI: 0.95-1.10), p=0.483 and HR=1.03 (CI: 0.98-1.07), p=0.230, respectively]. At 30, 90, 180, and 365 days, the c-index was 0.72 for log pro-BNP and 0.63 for LES (p=0.044). Pre-procedure log transform of plasma pro-BNP levels are an independent and strong predictor of short- and long-term outcomes after TAVI and are more discriminatory than LES. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Urodilatin, a natriuretic peptide with clinical implications.

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Meyer, M; Richter, R; Forssmann, W G

1998-02-21

Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also

Analytic validation and comparison of three commercial immunoassays for measurement of plasma atrial/A-type natriuretic peptide concentration in horses

DEFF Research Database (Denmark)

Trachsel, D S; Schwarzwald, C C; Grenacher, B

2014-01-01

Measurement of atrial/A-type natriuretic peptide (ANP) concentrations may be of use for assessment of cardiac disease, and reliable data on the analytic performance of available assays are needed. To assess the suitability for clinical use of commercially available ANP assays, intra-assay and inter......-Altman analyses. For all assays, precision was moderate but acceptable and dilution parallelism was good. All assays showed analytic performance similar to other immunoassays used in veterinary medicine. However, the results from the three assays were poorly comparable. Our study highlights the need...

B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease: Analysis from the EXCEL Trial.

Science.gov (United States)

Redfors, Björn; Chen, Shmuel; Crowley, Aaron; Ben-Yehuda, Ori; Gersh, Bernard J; Lembo, Nicholas J; Brown, W Morris; Banning, Adrian P; Taggart, David P; Serruys, Patrick W; Kappetein, Arie Pieter; Sabik, Joseph F; Stone, Gregg W

2018-04-17

Background -Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main (LM) CAD. Methods -The EXCEL trial randomized patients with LMCAD and low or intermediate SYNTAX scores to PCI with everolimus-eluting stents versus CABG. The primary endpoint was the composite of all-cause death, myocardial infarction (MI) or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. Results -BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower LVEF than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary endpoint (18.6% vs. 11.7%, adjusted HR 1.62, 95% CI 1.16-2.28, P=0.005), and higher mortality (11.5% vs. 3.9%, adjusted HR 2.49, 95% CI 1.48-4.19, P=0.0006), both from cardiovascular and non-cardiovascular causes. In contrast, there were no significant differences in the risks of MI, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction (P interaction =0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite endpoint at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG 1.54, 95% CI 0.96-2.47) versus normal BNP (adjusted HR 0.74, 95% CI 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a

Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells

Directory of Open Access Journals (Sweden)

van Benthem Jan

2010-01-01

Full Text Available Abstract Background Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC as compared to wild-type (WT cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM and γ-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU and vehicle were taken as controls. Results Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments. Conclusion These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.

Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism.

Science.gov (United States)

Dickey, Deborah M; Edmund, Aaron B; Otto, Neil M; Chaffee, Thomas S; Robinson, Jerid W; Potter, Lincoln R

2016-05-20

C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. Immunofluorescence microscopy also indicated that the mutant receptors were on the cell surface. All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

CD25+ B-1a Cells Express Aicda

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Hiroaki Kaku

2017-06-01

Full Text Available B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID, a product of the Aicda gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for Aicda in B-1a cells has been suggested on the basis of experiments with knock out (KO mice, whether B-1a cells express Aicda, and if so, which B-1a cell subpopulation expresses Aicda, remains unknown. Here, we demonstrate that B-1 cells express Aicda, but at a level below that expressed by germinal center (GC B cells. We previously reported that B-1a cells can be subdivided based on CD25 expression. We show here that B-1a cell Aicda expression is concentrated in the CD25+ B-1a cell subpopulation. These results suggest the possibility that previous studies of memory B cells identified on the basis of Aicda expression may have inadvertently included an unknown number of CD25+ B-1a cells. Although B-1a cells develop normally in the absence of Aicda, a competitive reconstitution assay reveals enhanced vigor for AID KO B-1a cell bone marrow (BM progenitors, as compared with wild-type BM B-1 cell progenitors. These results suggest that AID inhibits the development of B-1a cells from BM B-1 cell progenitors in a competitive environment.

Atrial natriuretic peptide and feeding activity patterns in rats

Directory of Open Access Journals (Sweden)

Oliveira M.H.A.

1997-01-01

Full Text Available This review presents historical data about atrial natriuretic peptide (ANP from its discovery as an atrial natriuretic factor (ANF to its role as an atrial natriuretic hormone (ANH. As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways

Anger Expression Types and Interpersonal Problems in Nurses.

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Han, Aekyung; Won, Jongsoon; Kim, Oksoo; Lee, Sang E

2015-06-01

The purpose of this study was to investigate the anger expression types in nurses and to analyze the differences between the anger expression types and interpersonal problems. The data were collected from 149 nurses working in general hospitals with 300 beds or more in Seoul or Gyeonggi province, Korea. For anger expression type, the anger expression scale from the Korean State-Trait Anger Expression Inventory was used. For interpersonal problems, the short form of the Korean Inventory of Interpersonal Problems Circumplex Scales was used. Data were analyzed using descriptive statistics, cluster analysis, multivariate analysis of variance, and Duncan's multiple comparisons test. Three anger expression types in nurses were found: low-anger expression, anger-in, and anger-in/control type. From the results of multivariate analysis of variance, there were significant differences between anger expression types and interpersonal problems (Wilks lambda F = 3.52, p interpersonal problems by Duncan's post hoc test (p interpersonal problems. Copyright © 2015. Published by Elsevier B.V.

Prognostic utility of the Seattle Heart Failure Score and amino terminal pro B-type natriuretic peptide in varying stages of systolic heart failure.

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Adlbrecht, Christopher; Hülsmann, Martin; Neuhold, Stephanie; Strunk, Guido; Pacher, Richard

2013-05-01

Cardiac transplantation represents the best procedure to improve long-term clinical outcome in advanced chronic heart failure (CHF), if pre-selection criteria are sufficient to outweigh the risk of the failing heart over the risk of transplantation. Although the cornerstone of success, risk assessment in heart transplant candidates is still under-investigated. Amino terminal pro B-type natriuretic peptide (NT-proBNP) is regarded as the best predictor of outcome in CHF, and the Seattle Heart Failure Score (SHFS), including clinical markers, is widely used if NT-proBNP is unavailable. The present study assessed the predictive value for all-cause death of the SHFS in CHF patients and compared it with NT-proBNP in a multivariate model including established baseline parameters known to predict survival. A total of 429 patients receiving stable HF-specific pharmacotherapy were included and monitored for 53.4 ± 20.6 months. Of these, 133 patients (31%) died during follow-up. Several established predictors of death on univariate analysis proved significant for the total study cohort. Systolic pulmonary arterial pressure (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.05); p < 0.001, Wald 15.1), logNT-proBNP (HR, 1.51; 95% CI, 1.22-1.86; p < 0.001, Wald 14.9), and the SHFS (HR, 0.99; 95% CI, 0.99-1.00; p < 0.001, Wald 12.6) remained within the stepwise multivariate Cox regression model as independent predictors of all-cause death. Receiver operating characteristic curve analysis revealed an area under the curve of 0.802 for logNT-proBNP and 0.762 for the SHFS. NT-proBNP is a more potent marker to identify patients at the highest risk. If the NT-proBNP measurement is unavailable, the SHFS may serve as an adequate clinical surrogate to predict all-cause death. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

cGMP inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland

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De Jonge, Hugo R.; Tilly, Ben C.; Hogema, Boris M.; Pfau, Daniel J.; Kelley, Catherine A.; Kelley, Megan H.; Melita, August M.; Morris, Montana T.; Viola, Ryan M.

2013-01-01

The in vitro perfused rectal gland of the dogfish shark (Squalus acanthias) and filter-grown monolayers of primary cultures of shark rectal gland (SRG) epithelial cells were used to analyze the signal transduction pathway by which C-type natriuretic peptide (CNP) stimulates chloride secretion. CNP binds to natriuretic receptors in the basolateral membrane, elevates cellular cGMP, and opens cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in the apical membrane. CNP-provoked chloride secretion was completely inhibitable by the nonspecific protein kinase inhibitor staurosporine and the PKA inhibitor H89 but insensitive to H8, an inhibitor of type I and II isoforms of cGMP-dependent protein kinase (cGKI and cGKII). CNP-induced secretion could not be mimicked by nonhydrolyzable cGMP analogs added alone or in combination with the protein kinase C activator phorbolester, arguing against a role for cGK or for cGMP-induced PKC signaling. We failed to detect a dogfish ortholog of cGKII by molecular cloning and affinity chromatography. However, inhibitors of the cGMP-inhibitable isoform of phosphodiesterase (PDE3) including milrinone, amrinone, and cilostamide but not inhibitors of other PDE isoenzymes mimicked the effect of CNP on chloride secretion in perfused glands and monolayers. CNP raised cGMP and cAMP levels in the SRG epithelial cells. This rise in cAMP as well as the CNP and amrinone-provoked chloride secretion, but not the rise in cGMP, was almost completely blocked by the Gαi-coupled adenylyl cyclase inhibitor somatostatin, arguing against a role for cGMP cross-activation of PKA in CNP action. These data provide molecular, functional, and pharmacological evidence for a CNP/cGMP/PDE3/cAMP/PKA signaling cascade coupled to CFTR in the SRG. PMID:24259420

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide.

Science.gov (United States)

Klaassen, Sebastiaan H C; Tromp, Jasper; Nienhuis, Hans L A; van der Meer, Peter; van den Berg, Maarten P; Blokzijl, Hans; van Veldhuisen, Dirk J; Hazenberg, Bouke P C

2018-01-01

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Plasmatic levels of N-terminal pro-atrial natriuretic peptide in preeclamptic patients and healthy normotensive pregnant women.

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Reyna-Villasmil, Eduardo; Mejia-Montilla, Jorly; Reyna-Villasmil, Nadia; Mayner-Tresol, Gabriel; Herrera-Moya, Pedro; Fernández-Ramírez, Andreina; Rondón-Tapía, Marta

2018-05-11

To compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women. A cases-controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected one hour after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters. Plasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26] pg/mL) showed a significant difference when compared with patients in group B (mean 0.55 [0.07] pg/mL; P<.001]. There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (P=ns). A cut-off value of 0.66ng/mL had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%. Preeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Atrial natriuretic factor receptor guanylate cyclase, ANF-RGC, transduces two independent signals, ANF and Ca2+

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Teresa eDuda

2014-03-01

Full Text Available Atrial natriuretic factor receptor guanylate cyclase, ANF-RGC, was the first discovered member of the mammalian membrane guanylate cyclase family. The hallmark feature of the family is that a single protein contains both the site for recognition of the regulatory signal and the ability to transduce it into the production of the second messenger, cyclic GMP. For over two decades, the family has been classified into two subfamilies, the hormone receptor subfamily with ANF-RGC being its paramount member, and the Ca2+ modulated subfamily, which includes the rod outer segment guanylate cyclases, ROS-GC1 and 2, and the olfactory neuroepithelial guanylate cyclase, ONE-GC. ANF-RGC is the receptor and the signal transducer of the most hypotensive hormones, atrial natriuretic factor (ANF and B-type natriuretic peptide (BNP. After binding these hormones at the extracellular domain it, at its intracellular domain, signals activation of the C-terminal catalytic module and accelerates the production of cyclic GMP. Cyclic GMP then serves the second messenger role in biological responses of ANF and BNP such as natriuresis, diuresis, vasorelaxation and anti-proliferation. Very recently another modus operandi for ANF-RGC was revealed. Its crux is that ANF-RGC activity is also regulated by Ca2+. The Ca2+ sensor neurocalcin  mediates this signaling mechanism. Strikingly, the Ca2+ and ANF signaling mechanisms employ separate structural motifs of ANF-RGC in modulating its core catalytic domain in accelerating the production of cyclic GMP. In this review the biochemistry and physiology of these mechanisms with emphasis on cardiovascular regulation will be discussed.

HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

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Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J; Chapman, Harold D; Serreze, David V; DiLorenzo, Teresa P

2018-04-09

Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles. Copyright © 2018 by The American Association of Immunologists, Inc.

Plant natriuretic peptides control of synthesis and systemic effects

KAUST Repository

Wang, Yuhua

2011-10-01

Plant natriuretic peptides (PNPs) are signaling molecules that are secreted into the apoplast particularly under conditions of biotic and abiotic stress. At the local level, PNPs modulate their own expression via feed forward and feedback loops to enable tuning of the response at the transcript and protein level and to prevent overexpression. PNPs also employ a systemic signal, possibly electrical, to rapidly alter photosynthesis and respiration not only in treated leaves but also in upper and lower leaves thereby modulating and integrating physiological responses at the level of the whole plant. © 2011 Landes Bioscience.

Effect of the renal natriuretic peptide, ularitide, alone or combined ...

African Journals Online (AJOL)

Effect of the renal natriuretic peptide, ularitide, alone or combined with ... inhibitor, Omapatrilat, on experimental volume overloadinduced congestive heart failure in ... N-terminal pro–brain natriuretic peptide (NT-proBNP) and high-sensitivity ...

Interaction of Body Mass Index on the Association Between N-Terminal-Pro-b-Type Natriuretic Peptide and Morbidity and Mortality in Patients With Acute Heart Failure: Findings From ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

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Bhatt, Ankeet S; Cooper, Lauren B; Ambrosy, Andrew P; Clare, Robert M; Coles, Adrian; Joyce, Emer; Krishnamoorthy, Arun; Butler, Javed; Felker, G Michael; Ezekowitz, Justin A; Armstrong, Paul W; Hernandez, Adrian F; O'Connor, Christopher M; Mentz, Robert J

2018-02-03

Higher body mass index (BMI) is associated with lower circulating levels of N-terminal-pro-b-type natriuretic peptide (NT-proBNP). The Interaction between BMI and NT-proBNP with respect to clinical outcomes is not well characterized in patients with acute heart failure. A total of 686 patients from the biomarker substudy of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated HF ) clinical trial with documented NT-proBNP levels at baseline were included in the present analysis. Patients were classified by the World Health Organization obesity classification (nonobese: BMI value of NT-proBNP was not modified by BMI in this acute heart failure population. NT-proBNP remains a useful prognostic indicator of long-term mortality in acute heart failure even in the obese patient. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

DEFF Research Database (Denmark)

Bartels, Emil D; Ploug, Thorkil; Størling, Joachim

2014-01-01

Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design. In t...... accumulation and attenuates peripheral insulin resistance in obese mice........ In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design...

[Natriuretic peptides. History of discovery, chemical structure, mechanism of action and the removal routes. Basis of diagnostic and therapeutic use].

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Stryjewski, Piotr J; Nessler, Bohdan; Cubera, Katarzyna; Nessler, Jadwiga

2013-01-01

Natriuretic peptides (NP) are the group of proteins synthesized and secreted by the mammalian heart. All the NP are synthesized from prohormones and have 17-amino acid cyclic structures containing two cysteine residues linked by internal disulphide bond. They are characterized by a wide range of actions, mainly through their membrane receptors. The NP regulate the water and electrolyte balance, blood pressure through their diuretic, natriuretic, and relaxating the vascular smooth muscles effects. They also affect the endocrine system and the nervous system. The neurohormonal regulation of blood circulation results are mainly based on antagonism with renin--angiotensin--aldosterone system. The NP representatives are: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), urodilatine and (DNP) Dendroaspis natriuretic peptide, not found in the human body. According to the guidelines of the European Society of Cardiology determination of NT-proBNP level have found a use in the diagnosis of acute and chronic heart failure, risk stratification in acute coronary syndromes and pulmonary embolism. There are reports found in the literature, that demonstrate the usefulness of NT-proBNP determination in valvular, atrial fibrillation, and syncopes. Recombinant human ANP--Carperitid and BNP--Nesiritid, have already found a use in the adjunctive therapy of dyspnea in acute heart failure.

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

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Broderick TL

2017-01-01

Full Text Available Tom L Broderick,1 Marek Jankowski,2 Jolanta Gutkowska2 1Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, Midwestern University, Glendale, AZ, USA; 2Department of Medicine, Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de l‘Université de Montréal-Hôtel-Dieu, Montréal, QC, Canada Background: Regular exercise training (ET and caloric restriction (CR are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT–natriuretic peptide (NP system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity. Methods: Five-week-old male db/db mice were assigned to the following groups: sedentary, ET, and ET + CR. Nonobese heterozygote littermates served as controls. ET was performed on a treadmill at moderate intensity, and CR was induced by reducing food intake by 30% of that consumed by sedentary db/db mice for a period of 8 weeks. Results: After 8 weeks, only ET + CR, but not ET, slightly improved body weight compared to sedentary db/db mice. Regardless of the treatment, db/db mice remained hyperglycemic. Hearts from db/db mice demonstrated reduced expression of genes linked to the cardiac OT–NP system. In fact, compared to control mice, mRNA expression of GATA binding protein 4 (GATA4, OT receptor, OT, brain NP, NP receptor type C, and endothelial nitric oxide synthase (eNOS was decreased in hearts from sedentary db/db mice. Both ET alone and ET + CR increased the mRNA expression of GATA4 compared to sedentary db/db mice. Only ET combined with CR produced increased eNOS mRNA and protein expression. Conclusion: Our data indicate that enhancement of eNOS by combined

B-type natriuretic peptide as predictor of heart failure in patients with acute ST elevation myocardial infarction, single-vessel disease, and complete revascularization: follow-up study.

LENUS (Irish Health Repository)

Manola, Sime

2012-01-31

AIM: To assess the concentration of B-type natriuretic peptide (BNP) as a predictor of heart failure in patients with acute ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) with successful and complete revascularization. METHODS: Out of a total of 220 patients with acute STEMI admitted to the Sisters of Mercy University Hospital in the period January 1 to December 31, 2007, only patients with acute STEMI undergoing primary PCI who had single vessel disease and were successfully revascularized were included in the study. Selected patients had no history of myocardial infarction or heart failure and a normal or near-normal left ventricular ejection fraction (> or =50%) assessed by left ventriculography at admission. Only 58 patients met the inclusion criteria for the study. Out of those, 6 patients refused to participate in the study, and another 5 could not be followed up, so a total of 47 patients were evaluated. Blood samples were taken for measurement of BNP levels at admission, 24 hours later, and 7 days later. Patients were followed up for 1 year. The primary outcome was reduction in left ventricular ejection fraction (LVEF) to <50% after 1 year. RESULTS: Patients who developed echocardiographic signs of reduced systolic function defined as LVEF<50% had significantly higher values of BNP (> or =80 pg\\/mL) at 24 hours (P=0.001) and 7 days (P=0.020) after STEMI and successful reperfusion. Patients who had BNP levels > or =80 pg\\/mL after 7 days were 21 times more likely to develop LVEF<50 (odds ratio, 20.8; 95% confidence interval, 2.2-195.2; P=0.008). CONCLUSION: BNP can be used as a predictor of reduced systolic function in patients with STEMI who underwent successful reperfusion and had normal ejection fraction at admission.

Relative Importance of History of Heart Failure Hospitalization and N-Terminal Pro-B-Type Natriuretic Peptide Level as Predictors of Outcomes in Patients With Heart Failure and Preserved Ejection Fraction.

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Kristensen, Søren L; Jhund, Pardeep S; Køber, Lars; McKelvie, Robert S; Zile, Michael R; Anand, Inder S; Komajda, Michel; Cleland, John G F; Carson, Peter E; McMurray, John J V

2015-06-01

The aim of this study was to investigate N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and recent heart failure (HF) hospitalization as predictors of future events in heart failure - preserved ejection fraction (HF-PEF). Recently, doubt has been expressed about the value of a history of HF hospitalization as a predictor of adverse cardiovascular outcomes in patients with HF and HF-PEF. We estimated rates and adjusted hazard ratios (HRs) for the composite endpoint of cardiovascular death or HF hospitalization, according to history of recent HF hospitalization and baseline NT-proBNP level in the I-PRESERVE (Irbesartan in Heart Failure with Preserved systolic function) trial. Rates of composite endpoints in patients with (n = 804) and without (n = 1,963) a recent HF hospitalization were 12.78 (95% confidence interval [CI]: 11.47 to 14.24) and 4.49 (95% CI: 4.04 to 4.99) per 100 person-years, respectively (HR: 2.71; 95% CI: 2.33 to 3.16). For patients with NT-proBNP concentrations >360 pg/ml (n = 1,299), the event rate was 11.51 (95% CI: 10.54 to 12.58) compared to 3.04 (95% CI: 2.63 to 3.52) per 100 person-years in those with a lower level of NT-proBNP (n = 1468) (HR: 3.19; 95% CI: 2.68 to 3.80). In patients with no recent HF hospitalization and NT-proBNP ≤360 pg/ml (n = 1,187), the event rate was 2.43 (95% CI: 2.03 to 2.90) compared with 17.79 (95% CI: 15.77 to 20.07) per 100 person-years when both risk predictors were present (n = 523; HR: 6.18; 95% CI: 4.96 to 7.69). Recent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

MicroRNA-10b expression in breast cancer and its clinical association.

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Jianhui Zhang

Full Text Available MicroRNAs (miRNAs are short non-coding RNA molecules that play a significant role in many types of cancers including breast cancer. In the current study, we evaluated the expression levels of microR-10b (miR-10b in 115 breast cancer patients from Sichuan Cancer Center. Real time reverse transcription-PCR was used to assess miR-10b expression. Clinical data including disease stage, survival status, age, ER/PR/HER2 status, molecular subtypes, tumor size, lymph node status and Ki-67 expression levels were correlated with miR-10b expression levels. Our data showed that the miR-10b expression is correlated with disease stage, living status and tumor sizes. We also found that miR-10b expression levels are higher in the lymph node positive group and the Ki-67 higher scoring group (score > 20. No statistically significant differences were observed based on age or molecular sub-type grouping. In conclusion, miR-10b may be a biomarker for breast cancer and is a potential treatment target.

C-type lectin B (SpCTL-B) regulates the expression of antimicrobial peptides and promotes phagocytosis in mud crab Scylla paramamosain.

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Wei, Xiaoyuan; Wang, Limin; Sun, Wanwei; Zhang, Ming; Ma, Hongyu; Zhang, Yueling; Zhang, Xinxu; Li, Shengkang

2018-07-01

As pattern recognition receptors, C-type lectins (CTLs) play important roles in immune system of crustaceans through identifying and binding to the conservative pathogen-associated molecular patterns (PAMPs) on pathogen surfaces. In this study, a new CTL, SpCTL-B, was identified from the hemocytes of mud crab Scylla paramamosain. The full-length of SpCTL-B cDNA was 1278 bp with an open reading frame (ORF) of 348 bp. The predicted SpCTL-B protein contains a single carbohydrate-recognition domain (CRD). SpCTL-B transcripts were distributed in all examined tissues with the highest levels in hepatopancreas. After challenged with Vibrio parahaemolyticus, LPS, polyI:C and white spot syndrome virus (WSSV), the mRNA levels of SpCTL-B in hemocytes and hepatopancreas were up-regulated. The recombinant SpCTL-B (rSpCTL-B) purified by Ni-affinity chromatography showed stronger binding activities with Staphylococcus aureus, β-hemolytic Streptococcus, Escherichia coli, Aeromonas hydrophila, Vibrio alginolyticus than those with V. parahaemolyticus and Saccharomyces cerevisiae. rSpCTL-B exhibited a broad spectrum of microorganism-agglutination activities against Gram-positive bacteria (S. aureus, β-hemolytic Streptococcus) and Gram-negative bacteria (E. coli, V. parahaemolyticus, A. hydrophila, V. alginolyticus) in a Ca 2+ -dependent manner. The agglutination activities of rSpCTL-B could be inhibited by D-mannose and LPS, but not by d-fructose and galactose. The antimicrobial assay showed that rSpCTL-B exhibited the growth inhibition against all examined gram-positive bacteria and gram-negative bacteria. When SpCTL-B was silenced by RNAi, the bacterial clearance ability in mud crab was decreased and the transcript levels of five antimicrobial peptides (AMPs) (SpCrustin, SpHistin, SpALF4 (anti-lipopolysaccharide factor), SpALF5 and SpALF6) were significantly decreased in hemocytes. In our study, knockdown of SpCTL-B could down-regulate the expression of SpSTAT at m

Combined use of brain natriuretic peptide and C-reactive protein for predicting cardiovascular risk in outpatients with type 2 diabetes mellitus

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Toshihiro Tsuruda

2007-09-01

Full Text Available Toshihiro Tsuruda1, Johji Kato2, Takahiro Sumi1, Kazuya Mishima1, Hiroyuki Masuyama1, Hiroyuki Nakao3, Takuroh Imamura1, Tanenao Eto1, Kazuo Kitamura11Department of Internal Medicine, Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; 2Frontier Research Center, University of Miyazaki, Miyazaki, Japan; 3Department of Public Health, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan Abstract: Appropriate tools are necessary for predicting cardiovascular events in patients with diabetes mellitus because of their high incidence. In this study, we assessed whether a combination of brain natriuretic peptide (BNP and C-reactive protein (CRP measurement were useful prognosticators in patients with type 2 diabetes mellitus. One hundred and nine patients with type 2 diabetes mellitus, aged 52 to 93 years, were examined at outpatient clinics for blood, urinary samples, and echocardiography. They were then followed prospectively. During the average follow-up period of 30 months (range, 3 to 37, 15 patients (14% had cardiovascular events: This was the first event in 5 patients and a recurrence in 10. Cox regression analysis showed that the past event (hazard ratio [HR] 4.819 [95% confidence interval (CI: 1.299–17.881]; p = 0.019 and plasma BNP level (HR 1.007 [95% CI: 1.002–1.012]; p = 0.010] were independently significant factors for the cardiovascular events during the follow-up period. Patients with plasma BNP ≥53 pg/mL and CRP ≥0.95 mg/dL demonstrated the highest incidence in cardiovascular event, compared to those categorized into either or both low levels of BNP and CRP. This study suggests that combination of plasma BNP and CRP measurement provides the additive prognostic information of cardiovascular events in patients with type 2 diabetes mellitus.Keywords: diabetes mellitus; natriuretic peptide; inflammation; mortality and morbidity

Influenza A virus inhibits type I IFN signaling via NF-kappaB-dependent induction of SOCS-3 expression.

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Eva-K Pauli

2008-11-01

Full Text Available The type I interferon (IFN system is a first line of defense against viral infections. Viruses have developed various mechanisms to counteract this response. So far, the interferon antagonistic activity of influenza A viruses was mainly observed on the level of IFNbeta gene induction via action of the viral non-structural protein 1 (NS1. Here we present data indicating that influenza A viruses not only suppress IFNbeta gene induction but also inhibit type I IFN signaling through a mechanism involving induction of the suppressor of cytokine signaling-3 (SOCS-3 protein. Our study was based on the observation that in cells that were infected with influenza A virus and subsequently stimulated with IFNalpha/beta, phosphorylation of the signal transducer and activator of transcription protein 1 (STAT1 was strongly reduced. This impaired STAT1 activation was not due to the action of viral proteins but rather appeared to be induced by accumulation of viral 5' triphosphate RNA in the cell. SOCS proteins are potent endogenous inhibitors of Janus kinase (JAK/STAT signaling. Closer examination revealed that SOCS-3 but not SOCS-1 mRNA levels increase in an RNA- and nuclear factor kappa B (NF-kappaB-dependent but type I IFN-independent manner early in the viral replication cycle. This direct viral induction of SOCS-3 mRNA and protein expression appears to be relevant for suppression of the antiviral response since in SOCS-3 deficient cells a sustained phosphorylation of STAT1 correlated with elevated expression of type I IFN-dependent genes. As a consequence, progeny virus titers were reduced in SOCS-3 deficient cells or in cells were SOCS-3 expression was knocked-down by siRNA. These data provide the first evidence that influenza A viruses suppress type I IFN signaling on the level of JAK/STAT activation. The inhibitory effect is at least in part due to the induction of SOCS-3 gene expression, which results in an impaired antiviral response.

Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells

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Takachi, Takayuki; Takahashi, Masahiko; Takahashi-Yoshita, Manami; Higuchi, Masaya; Obata, Miki; Mishima, Yukio; Okuda, Shujiro; Tanaka, Yuetsu; Matsuoka, Masao; Saitoh, Akihiko; Green, Patrick L; Fujii, Masahiro

2015-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells. PMID:25613934

Family with sequence similarity 83, member B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild-type epidermal growth factor receptor.

Science.gov (United States)

Yamaura, Takumi; Ezaki, Junji; Okabe, Naoyuki; Takagi, Hironori; Ozaki, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Muto, Satoshi; Matsumura, Yuki; Hasegawa, Takeo; Hoshino, Mika; Osugi, Jun; Shio, Yutaka; Waguri, Satoshi; Tamura, Hirosumi; Imai, Jun-Ichi; Ito, Emi; Yanagisawa, Yuka; Honma, Reiko; Watanabe, Shinya; Suzuki, Hiroyuki

2018-02-01

Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor ( EGFR ) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B ( FAM83B ) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated. Matched tumor and adjacent normal tissue samples were obtained from 216 patients who underwent complete lung resection for primary lung ADC and were examined for FAM83B expression using cDNA microarray analysis. The associations between FAM83B expression and clinicopathological parameters, including patient survival, were examined. FAM83B was highly expressed in tumors from males, smokers and in tumors with wild-type EGFR . Multivariate analyses further confirmed that wild-type EGFR tumors were significantly positively associated with FAM83B expression. In survival analysis, FAM83B expression was associated with poor outcomes in disease-free survival and overall survival, particularly when stratified against tumors with wild-type EGFR . Furthermore, FAM83B knockdown was performed to investigate its phenotypic effect on lung ADC cell lines. Gene silencing by FAM83B RNA interference induced growth suppression in the HLC-1 and H1975 lung ADC cell lines. FAM83B may be involved in lung ADC tumor proliferation and can be a predictor of poor survival. FAM83B is also a potential novel therapeutic target for ADC with wild-type EGFR .

NF-kappaB signaling mediates vascular smooth muscle endothelin type B receptor expression in resistance arteries

DEFF Research Database (Denmark)

Zheng, Jian-Pu; Zhang, Yaping; Edvinsson, Lars

2010-01-01

Vascular smooth muscle cells (SMC) endothelin type B (ET(B)) receptor upregulation results in strong vasoconstriction and reduction of local blood flow. We hypothesizes that the underlying molecular mechanisms involve transcriptional factor nuclear factor-kappaB (NF-kappaB) pathway. ET(B) recepto...

Brain natriuretic peptide:Much more than a biomarker

OpenAIRE

Calzetta, Luigino; Orlandi, Augusto; Page, Clive; Rogliani, Paola; Rinaldi, Barbara; Rosano, Giuseppe; Cazzola, Mario; Matera, Maria Gabriella

2016-01-01

Brain natriuretic peptide (BNP) modulates several biological processes by activating the natriuretic peptide receptor A (NPR-A). Atria and ventricles secrete BNP. BNP increases natriuresis, diuresis and vasodilatation, thus resulting in a decreased cardiac workload. BNP and NT-proBNP, which is the biologically inactive N-terminal portion of its pro-hormone, are fast and sensitive biomarkers for diagnosing heart failure. The plasma concentrations of both BNP and NT-proBNP also correlate with l...

Natriuretic peptides in unstable coronary artery disease.

Science.gov (United States)

Jernberg, Tomas; James, Stefan; Lindahl, Bertil; Johnston, Nina; Stridsberg, Mats; Venge, Per; Wallentin, Lars

2004-09-01

Patients with unstable coronary artery disease (CAD), i.e., unstable angina or non-ST-elevation myocardial infarction, vary widely in clinical presentation, prognosis and response to treatment. To select appropriate therapy, early risk stratification has become increasingly important. This review focuses on the emerging role of natriuretic peptides in the early assessment of patients with unstable CAD. We conclude that levels of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are strongly associated to mortality and the risk of future congestive heart failure, and carry important prognostic information independent from previously known risk factors in unstable CAD. There are some data indicating that these markers can also be helpful in the selection of appropriate therapy in these patients but further studies are needed. Before a routine use of BNP or NT-proBNP in unstable CAD can be recommended, the cost-effectiveness of adding these new markers to the currently routine markers and their impact on selection of treatment needs further evaluation. Copyright 2004 Elsevier Ltd

Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

Science.gov (United States)

Battes, Linda C; Caliskan, Kadir; Rizopoulos, Dimitris; Constantinescu, Alina A; Robertus, Jan L; Akkerhuis, Martijn; Manintveld, Olivier C; Boersma, Eric; Kardys, Isabella

2015-03-01

Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

B cell lymphomas express CX3CR1 a non-B cell lineage adhesion molecule

DEFF Research Database (Denmark)

Andreasson, U.; Ek, S.; Merz, H.

2008-01-01

normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma......To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering...... the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which...

Molecular cloning, genomic organization, and expression of a B-type (cricket-type) allatostatin preprohormone from Drosophila melanogaster

DEFF Research Database (Denmark)

Williamson, M; Lenz, C; Winther, A M

2001-01-01

and nonamidated C terminus. We have previously reported the structure of an A-type allatostatin preprohormone from the fruitfly Drosophila melanogaster. Here we describe the molecular cloning of a B-type prepro-allatostatin from Drosophila (DAP-B). DAP-B is 211 amino acid residues long and contains one copy each...

Natriuretic peptides and cerebral hemodynamics

DEFF Research Database (Denmark)

Guo, Song; Barringer, Filippa; Zois, Nora Elisabeth

2014-01-01

Natriuretic peptides have emerged as important diagnostic and prognostic tools for cardiovascular disease. Plasma measurement of the bioactive peptides as well as precursor-derived fragments is a sensitive tool in assessing heart failure. In heart failure, the peptides are used as treatment...... in decompensated disease. In contrast, their biological effects on the cerebral hemodynamics are poorly understood. In this mini-review, we summarize the hemodynamic effects of the natriuretic peptides with a focus on the cerebral hemodynamics. In addition, we will discuss its potential implications in diseases...... where alteration of the cerebral hemodynamics plays a role such as migraine and acute brain injury including stroke. We conclude that a possible role of the peptides is feasible as evaluated from animal and in vitro studies, but more research is needed in humans to determine the precise response...

Postreplication Roles of the Brucella VirB Type IV Secretion System Uncovered via Conditional Expression of the VirB11 ATPase

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Erin P. Smith

2016-11-01

Full Text Available Brucella abortus, the bacterial agent of the worldwide zoonosis brucellosis, primarily infects host phagocytes, where it undergoes an intracellular cycle within a dedicated membrane-bound vacuole, the Brucella-containing vacuole (BCV. Initially of endosomal origin (eBCV, BCVs are remodeled into replication-permissive organelles (rBCV derived from the host endoplasmic reticulum, a process that requires modulation of host secretory functions via delivery of effector proteins by the Brucella VirB type IV secretion system (T4SS. Following replication, rBCVs are converted into autophagic vacuoles (aBCVs that facilitate bacterial egress and subsequent infections, arguing that the bacterium sequentially manipulates multiple cellular pathways to complete its cycle. The VirB T4SS is essential for rBCV biogenesis, as VirB-deficient mutants are stalled in eBCVs and cannot mediate rBCV biogenesis. This has precluded analysis of whether the VirB apparatus also drives subsequent stages of the Brucella intracellular cycle. To address this issue, we have generated a B. abortus strain in which VirB T4SS function is conditionally controlled via anhydrotetracycline (ATc-dependent complementation of a deletion of the virB11 gene encoding the VirB11 ATPase. We show in murine bone marrow-derived macrophages (BMMs that early VirB production is essential for optimal rBCV biogenesis and bacterial replication. Transient expression of virB11 prior to infection was sufficient to mediate normal rBCV biogenesis and bacterial replication but led to T4SS inactivation and decreased aBCV formation and bacterial release, indicating that these postreplication stages are also T4SS dependent. Hence, our findings support the hypothesis of additional, postreplication roles of type IV secretion in the Brucella intracellular cycle.

B-cell-intrinsic hepatitis C virus expression leads to B-cell-lymphomagenesis and induction of NF-κB signalling.

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Yuri Kasama

Full Text Available Hepatitis C virus (HCV infection leads to the development of hepatic diseases, as well as extrahepatic disorders such as B-cell non-Hodgkin's lymphoma (B-NHL. To reveal the molecular signalling pathways responsible for HCV-associated B-NHL development, we utilised transgenic (Tg mice that express the full-length HCV genome specifically in B cells and develop non-Hodgkin type B-cell lymphomas (BCLs. The gene expression profiles in B cells from BCL-developing HCV-Tg mice, from BCL-non-developing HCV-Tg mice, and from BCL-non-developing HCV-negative mice were analysed by genome-wide microarray. In BCLs from HCV-Tg mice, the expression of various genes was modified, and for some genes, expression was influenced by the gender of the animals. Markedly modified genes such as Fos, C3, LTβR, A20, NF-κB and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-κB signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.

Antihypertensive action of non-natriuretic doses of furosemide in Dahl salt-sensitive rats

DEFF Research Database (Denmark)

Haugan, Ketil; Petersen, Jørgen Søberg; Spannow, Jesper

1997-01-01

Farmakologi, blood pressure, Dahl rats, furosemide, sodium balance, total body sodium, non-natriuretic......Farmakologi, blood pressure, Dahl rats, furosemide, sodium balance, total body sodium, non-natriuretic...

Atrial cardiomyocyte-specific expression of Cre recombinase driven by an Nppa gene fragment

NARCIS (Netherlands)

de Lange, Frederik J.; Moorman, Antoon F. M.; Christoffels, Vincent M.

2003-01-01

To study the development of the atria, we produced a transgenic mouse line that expresses Cre under the regulatory control of a 7 kbp fragment of the Natriuretic peptide precursor type A gene (Nppa), from -3 kbp to +4 kbp relative to the transcription start site. Crossing this line with the R26R and

[Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease].

Science.gov (United States)

Higueras, Javier; Martín-Ventura, José Luis; Blanco-Colio, Luis; Cristóbal, Carmen; Tarín, Nieves; Huelmos, Ana; Alonso, Joaquín; Pello, Ana; Aceña, Álvaro; Carda, Rocío; Lorenzo, Óscar; Mahíllo-Fernández, Ignacio; Asensio, Dolores; Almeida, Pedro; Rodríguez-Artalejo, Fernando; Farré, Jerónimo; López Bescós, Lorenzo; Egido, Jesús; Tuñón, José

2015-01-01

At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population. To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD. A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 ± 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); Pvalue improved with an area under the curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P<0.001, log -rank test). Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Increased plasma concentrations of midregional proatrial natriuretic Peptide is associated with risk of cardiorenal dysfunction in type 1 diabetes

DEFF Research Database (Denmark)

Theilade, Simone; Hansen, Tine Willum; Goetze, Jens Peter

2015-01-01

BACKGROUND: To examine possible associations between midregional proatrial natriuretic peptide (MR-proANP) and diabetic complications at baseline and risk of mortality and end-stage renal disease (ESRD) during follow-up in type 1 diabetes. METHODS: Observational study including 667 patients...... = 369), and retinopathy (n = 523). Adjustments included gender, age, systolic blood pressure, estimated glomerular filtration rate (eGFR), UAER, HbA1c, total cholesterol, 24-hour urinary sodium excretion (24h-U(Na)), body mass index, daily insulin dose, antihypertensive treatment, and smoking in linear...... regression analyses and analysis of covariance models. Development of ESRD (dialysis, renal transplantation, or GFR/eGFR 2)) and mortality was recorded through national registers. RESULTS: The cohort included 293 (44%) females, aged 55 ± 13 years. Plasma MR-proANP (median (interquartile...

Mid-regional pro-atrial natriuretic peptide and blood pressure in adolescents

DEFF Research Database (Denmark)

Goharian, Tina S; Gimsing, Anders N; Goetze, Jens P

2015-01-01

Little is known about blood pressure in relation to circulating natriuretic peptide concentrations and gender in generally healthy adolescents. We studied 15-year-old females and males (n = 335) from the Danish site of the European Youth Heart Study (EYHS). Blood pressure was measured using...... a standardized protocol, sexual maturity was assessed according to Tanner stage, and as a surrogate for atrial natriuretic peptide, we measured mid-regional pro-atrial natriuretic peptide (MR-proANP) in plasma. Compared with boys, girls had lower systolic blood pressure (SBP) (mean ± SD: 109.6 ± 9.9 mmHg vs 116.......9 ± 11.4 mmHg, p blood pressure...

Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

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Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

2018-01-01

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

Inhibition of dehydration-induced water intake by glucocorticoids is associated with activation of hypothalamic natriuretic peptide receptor-A in rat.

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Chao Liu

Full Text Available Atrial natriuretic peptide (ANP provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A, is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of

Triiodothyronine and brain natriuretic peptide: similar long-term prognostic values for chronic heart failure.

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Kozdag, Guliz; Ertas, Gokhan; Kilic, Teoman; Acar, Eser; Sahin, Tayfun; Ural, Dilek

2010-01-01

Although low levels of free triiodothyronine and high levels of brain natriuretic peptide have been shown as independent predictors of death in chronic heart failure patients, few studies have compared their prognostic values. The aim of this prospective study was to measure free triiodothyronine and brain natriuretic peptide levels and to compare their prognostic values among such patients.A total of 334 patients (mean age, 62 ± 13 yr; 218 men) with ischemic and nonischemic dilated cardiomyopathy were included in the study. The primary endpoint was a major cardiac event.During the follow-up period, 92 patients (28%) experienced a major cardiac event. Mean free triiodothyronine levels were lower and median brain natriuretic peptide levels were higher in patients with major cardiac events than in those without. A significant negative correlation was found between free triiodothyronine and brain natriuretic peptide levels. Receiver operating characteristic curve analysis showed that the predictive cutoff values were triiodothyronine and > 686 pg/mL for brain natriuretic peptide. Cumulative survival was significantly lower among patients with free triiodothyronine 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide.In the present study, free triiodothyronine and brain natriuretic peptide had similar prognostic values for predicting long-term prognosis in chronic heart failure patients. These results also suggested that combining these biomarkers may provide an important risk indicator for patients with heart failure.

Brain natriuretic peptide: Much more than a biomarker.

Science.gov (United States)

Calzetta, Luigino; Orlandi, Augusto; Page, Clive; Rogliani, Paola; Rinaldi, Barbara; Rosano, Giuseppe; Cazzola, Mario; Matera, Maria Gabriella

2016-10-15

Brain natriuretic peptide (BNP) modulates several biological processes by activating the natriuretic peptide receptor A (NPR-A). Atria and ventricles secrete BNP. BNP increases natriuresis, diuresis and vasodilatation, thus resulting in a decreased cardiac workload. BNP and NT-proBNP, which is the biologically inactive N-terminal portion of its pro-hormone, are fast and sensitive biomarkers for diagnosing heart failure. The plasma concentrations of both BNP and NT-proBNP also correlate with left ventricular function in patients with acute exacerbation of COPD, even without history of heart failure. Several studies have been conducted in vitro and in vivo, both in animals and in humans, in order to assess the potential role of the NPR-A activation as a novel therapeutic approach for treating obstructive pulmonary disorders. Unfortunately, these studies have yielded conflicting results. Nevertheless, further recent specific studies, performed in ex vivo models of asthma and COPD, have confirmed the bronchorelaxant effect of BNP and its protective role against bronchial hyperresponsiveness in human airways. These studies have also clarified the intimate mechanism of action of BNP, represented by an autocrine loop elicited by the activation of NPR-A, localized on bronchial epithelium, and the relaxant response of the surrounding ASM, which does not expresses NPR-A. This review explores the teleological activities and paradoxical effects of BNP with regard to chronic obstructive respiratory disorders, and provides an excursus on the main scientific findings that explain why BNP should be considered much more than a biomarker. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Different natriuretic responses in obese and lean rats in response to nitric oxide reduction.

Science.gov (United States)

Ambrozewicz, Marta A; Khraibi, Ali A; Simsek-Duran, Fatma; DeBose, Sophia C; Baydoun, Hind A; Dobrian, Anca D

2011-08-01

Nitric oxide (NO) is an important regulator of renal sodium transport and participates in the control of natriuresis and diuresis. In obesity, the nitric oxide bioavailability was reportedly reduced, which may contribute to the maintenance of hypertension. The aim of this study was to determine the effect of NO depletion on renal sodium handling in a model of diet-induced obesity hypertension. Obese hypertensive (obesity-prone (OP)) and lean normotensive (obesity-resistant (OR)) Sprague-Dawley rats were treated with 1.2 mg/kg/day N(G)-nitro-L-arginine-methyl ester (L-NAME) for 4 weeks to inhibit NO synthesis. Acute pressure natriuresis and diuresis were measured in response to an increase in perfusion pressure. NHE3 and Na(+), K(+)-ATPase protein expression were measured by Western blot and NHE3 activity was determined as the rate of pH change in brush border membrane vesicles. NHE3 membrane localization was determined by confocal microscopy. L-NAME did not significantly attenuate the natriuretic and diuretic responses to increases in renal perfusion pressure (RPP) in OP rats while inducing a significant reduction in OR rats. Following chronic NO inhibition, NHE3 protein expression and activity and Na(+), K(+)-ATPase protein expression were significantly increased in the OR but not in the OP group. Immunofluorescence studies indicated that the increase in NHE3 activity could be, at least in part, due to NHE3 membrane trafficking. Obese hypertensive rats have a weaker natriuretic response in response to NO inhibition compared to lean rats and the mechanism involves different regulation of the apical sodium exchanger NHE3 expression, activity, and trafficking.

DMPD: The atrial natriuretic peptide regulates the production of inflammatorymediators in macrophages. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 11890659 The atrial natriuretic peptide regulates the production of inflammatorymed...tml) (.csml) Show The atrial natriuretic peptide regulates the production of inflammatorymediators in macrop...hages. PubmedID 11890659 Title The atrial natriuretic peptide regulates the produ

Recombinant Expression and Purification of the Shigella Translocator IpaB.

Science.gov (United States)

Barta, Michael L; Adam, Philip R; Dickenson, Nicholas E

2017-01-01

Type III secretion systems (T3SS) are highly conserved virulence factors employed by a large number of pathogenic gram-negative bacteria. Like many T3SS translocators, recombinant expression of the hydrophobic Shigella protein IpaB requires the presence of its cognate chaperone IpgC. Chaperone-bound IpaB is maintained in a nonfunctional state, which has hampered in vitro studies aimed at understanding molecular structure and function of this important class of T3SS proteins. Herein, we describe an expression and purification protocol that utilizes mild detergents to produce highly purified, homogeneous IpaB of defined oligomeric states.

B-type natriuretic peptide measurement in primary care; magnitude of associations with cardiovascular risk factors and their therapies. Observations from the STOP-HF (St. Vincent's Screening TO Prevent Heart Failure) study.

LENUS (Irish Health Repository)

Conlon, Carmel M

2012-02-01

BACKGROUND: An effective prevention strategy for heart failure in primary care requires a reliable screening tool for asymptomatic ventricular dysfunction. Preliminary data indicate that B-type natriuretic peptide (BNP) may be suitable for this task. However, for the most effective use of this peptide, the interrelationships between associated risk factors and their therapies on BNP, and in particular their magnitude of effect, needs to be established in a large primary care population. Therefore, the objective of the study was to establish the extent of the association between BNP, cardiovascular risk factors and their therapies. METHODS: BNP measurement and clinical review was preformed on 1122 primary care patients with cardiovascular risk factors. Multivariate analyses identified significant associates of BNP concentrations which were further explored to establish the magnitude of their association. RESULTS: Associates of BNP were age (1.36-fold increase in BNP\\/decade), female (1.28), beta-blockers (1.90), myocardial infarction (1.36), arrhythmia (1.98), diastolic blood pressure; all p<0.01. A novel method was devised that plotted median BNP per sliding decade of age for the various combinations of these principal associates. CONCLUSIONS: The data presented underline the importance of considering several clinical and therapeutic factors when interpreting BNP concentrations. Most of these variables were associated with increased concentrations, which may in part explain the observed false-positive rates for detecting ventricular dysfunction using this peptide. Furthermore, the design of studies or protocols using BNP as an endpoint or a clinical tool should take particular account of these associations. This analysis provides the foundation for age, risk factor and therapy adjusted reference ranges for BNP in this setting.

Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes : The ADVANCE Trial

NARCIS (Netherlands)

Ohkuma, Toshiaki; Jun, Min; Woodward, Mark; Zoungas, Sophia; Cooper, Mark E; Grobbee, Diederick E; Hamet, Pavel; Mancia, Giuseppe; Williams, Bryan; Welsh, Paul; Sattar, Naveed; Shaw, Jonathan E.; Rahimi, Kazem; Chalmers, John

OBJECTIVE: This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes.

Postoperative B-Type Natriuretic Peptide as Predictor for Postoperative Outcomes in Patients Implanted With Left Ventricular Assist Devices.

Science.gov (United States)

Yost, Gardner; Bhat, Geetha; Pappas, Patroklos; Tatooles, Antone

2018-04-18

Brain natriuretic peptide (BNP) is a cardiac neurohormone known to correlate with left ventricular (LV) dilation, decreased contractility, and increased stiffness. Consequently, BNP has been used as a prognostic tool to assess the degree of LV unloading for patients supported by continuous-flow LV assist devices (LVADs). We assessed the prognostic value of changes in BNP in the 2 weeks after LVAD implantation. This retrospective study analyzed laboratory findings and outcomes of 189 LVAD patients. Patients were separated into two groups based on whether serum BNP levels had improved from preoperative levels by postoperative day 14. Group 1 had improvement in BNP levels, whereas group 2 had no improvement or worsening in BNP. There were no significant differences between the groups in age, gender, race, body mass index, or comorbidities. Group 1 had preoperative BNP 1,125 ± 1,078.3 pg/dl and postoperative BNP 440.2 ± 267.7 pg/dl (ΔBNP = -693.09 ± 942.4 pg/dl), whereas group 2 had preoperative BNP 346.0 ± 309.1 pg/dl and postoperative BNP 631.57 ± 483.4 pg/dl (ΔBNP = 289.32 ± 329.7 pg/dl). Postoperative survival in group 2 was significantly worse than in group 1. Rates of right ventricular failure (RVF) were significantly higher in group 2 (group 1: 39%, group 2: 52.7%; p = 0.01). In most patients implanted with a LVAD, BNP improves significantly in the postoperative period as the LV is unloaded. Our results indicate that lack of improvement in postoperative BNP is associated with longer length of stay, increased rates of RVF, and is an independent risk factor for reduced postoperative survival.

Practical use of natriuretic peptide measurement: questionnaire results from general practitioners and cardiologists.

Science.gov (United States)

Husby, Simon; Lind, Bent; Goetze, Jens P

2012-02-01

To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) measurement among doctors using this biomarker. We performed a questionnaire-based study on the use of BNP/NT-proBNP measurement among doctors; 21 general practitioners and 23 randomly chosen doctors at cardiology departments were interviewed. 12 general practitioners (57%) answered 'yes', eight (38%) answered 'no' and one (5%) was 'undecided' for use of BNP/NT-proBNP measurement to exclude a diagnosis of heart failure. Among cardiologists, 11 (48%) answered 'yes', ten (43%) answered 'no' and two (9%) were 'undecided' (no difference between groups, p = 0.56). The majority of doctors were familiar with BNP/NT-proBNP being affected by age but were unaware of the impact of gender and obesity. We propose that BNP/NT-proBNP measurement results should be supplied with age- and gender-related cut-off values, along with a notion of the negative predictive value and other parameters affecting the concentration in plasma.

Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

Directory of Open Access Journals (Sweden)

Florie Desriac

2018-04-01

Full Text Available We have previously shown that the C-type Natriuretic Peptide (CNP, a peptide produced by lungs, is able to impact Pseudomonas aeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention.

Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume.

Science.gov (United States)

Grassini, Daniela R; Lagendijk, Anne K; De Angelis, Jessica E; Da Silva, Jason; Jeanes, Angela; Zettler, Nicole; Bower, Neil I; Hogan, Benjamin M; Smith, Kelly A

2018-05-11

Atrial natriuretic peptide ( nppa/anf ) and brain natriuretic peptide ( nppb/bnp ) form a gene cluster with expression in the chambers of the developing heart. Despite restricted expression, a function in cardiac development has not been demonstrated by mutant analysis. This is attributed to functional redundancy however their genomic location in cis has impeded formal analysis. Using genome-editing, we generated mutants for nppa and nppb and found single mutants indistinguishable from wildtype whereas nppa / nppb double mutants display heart morphogenesis defects and pericardial oedema. Analysis of atrioventricular canal (AVC) markers show expansion of bmp4 , tbx2b, has2 and versican expression into the atrium of double mutants. This expanded expression correlates with increased extracellular matrix in the atrium. Using a biosensor for Hyaluronic acid to measure the cardiac jelly (cardiac extracellular matrix), we confirm cardiac jelly expansion in nppa / nppb double mutants. Finally, bmp4 knockdown rescues the expansion of has2 expression and cardiac jelly in double mutants. This definitively shows that nppa and nppb function redundantly during cardiac development to restrict gene expression to the AVC, preventing excessive cardiac jelly synthesis in the atrial chamber. © 2018. Published by The Company of Biologists Ltd.

Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats.

Science.gov (United States)

Wurtinger, Gabriel; Henrich, Estelle; Hildebrandt, Nicolai; Wiedemann, Nicola; Schneider, Matthias; Hassdenteufel, Esther

2017-12-20

Cats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion. Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions. Six cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion. POC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

Effectiveness and cost-effectiveness of serum B-type natriuretic peptide testing and monitoring in patients with heart failure in primary and secondary care: an evidence synthesis, cohort study and cost-effectiveness model.

Science.gov (United States)

Pufulete, Maria; Maishman, Rachel; Dabner, Lucy; Mohiuddin, Syed; Hollingworth, William; Rogers, Chris A; Higgins, Julian; Dayer, Mark; Macleod, John; Purdy, Sarah; McDonagh, Theresa; Nightingale, Angus; Williams, Rachael; Reeves, Barnaby C

2017-08-01

Heart failure (HF) affects around 500,000 people in the UK. HF medications are frequently underprescribed and B-type natriuretic peptide (BNP)-guided therapy may help to optimise treatment. To evaluate the clinical effectiveness and cost-effectiveness of BNP-guided therapy compared with symptom-guided therapy in HF patients. Systematic review, cohort study and cost-effectiveness model. A literature review and usual care in the NHS. (a) HF patients in randomised controlled trials (RCTs) of BNP-guided therapy; and (b) patients having usual care for HF in the NHS. Systematic review : BNP-guided therapy or symptom-guided therapy in primary or secondary care. Cohort study : BNP monitored (≥ 6 months' follow-up and three or more BNP tests and two or more tests per year), BNP tested (≥ 1 tests but not BNP monitored) or never tested. Cost-effectiveness model : BNP-guided therapy in specialist clinics. Mortality, hospital admission (all cause and HF related) and adverse events; and quality-adjusted life-years (QALYs) for the cost-effectiveness model. Systematic review : Individual participant or aggregate data from eligible RCTs. Cohort study : The Clinical Practice Research Datalink, Hospital Episode Statistics and National Heart Failure Audit (NHFA). A systematic literature search (five databases, trial registries, grey literature and reference lists of publications) for published and unpublished RCTs. Five RCTs contributed individual participant data (IPD) and eight RCTs contributed aggregate data (1536 participants were randomised to BNP-guided therapy and 1538 participants were randomised to symptom-guided therapy). For all-cause mortality, the hazard ratio (HR) for BNP-guided therapy was 0.87 [95% confidence interval (CI) 0.73 to 1.04]. Patients who were aged Chris A Rogers' and Maria Pufulete's time contributing to the study. Syed Mohiuddin's time is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West at University

Bartonella henselae trimeric autotransporter adhesin BadA expression interferes with effector translocation by the VirB/D4 type IV secretion system.

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Lu, Yun-Yueh; Franz, Bettina; Truttmann, Matthias C; Riess, Tanja; Gay-Fraret, Jérémie; Faustmann, Marco; Kempf, Volkhard A J; Dehio, Christoph

2013-05-01

The Gram-negative, zoonotic pathogen Bartonella henselae is the aetiological agent of cat scratch disease, bacillary angiomatosis and peliosis hepatis in humans. Two pathogenicity factors of B. henselae - each displaying multiple functions in host cell interaction - have been characterized in greater detail: the trimeric autotransporter Bartonella adhesin A (BadA) and the type IV secretion system VirB/D4 (VirB/D4 T4SS). BadA mediates, e.g. binding to fibronectin (Fn), adherence to endothelial cells (ECs) and secretion of vascular endothelial growth factor (VEGF). VirB/D4 translocates several Bartonella effector proteins (Beps) into the cytoplasm of infected ECs, resulting, e.g. in uptake of bacterial aggregates via the invasome structure, inhibition of apoptosis and activation of a proangiogenic phenotype. Despite this knowledge of the individual activities of BadA or VirB/D4 it is unknown whether these major virulence factors affect each other in their specific activities. In this study, expression and function of BadA and VirB/D4 were analysed in a variety of clinical B. henselae isolates. Data revealed that most isolates have lost expression of either BadA or VirB/D4 during in vitro passages. However, the phenotypic effects of coexpression of both virulence factors was studied in one clinical isolate that was found to stably coexpress BadA and VirB/D4, as well as by ectopic expression of BadA in a strain expressing VirB/D4 but not BadA. BadA, which forms a dense layer on the bacterial surface, negatively affected VirB/D4-dependent Bep translocation and invasome formation by likely preventing close contact between the bacterial cell envelope and the host cell membrane. In contrast, BadA-dependent Fn binding, adhesion to ECs and VEGF secretion were not affected by a functional VirB/D4 T4SS. The obtained data imply that the essential virulence factors BadA and VirB/D4 are likely differentially expressed during different stages of the infection cycle of

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

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Salah, Khibar; Pinto, Yigal M; Eurlings, Luc W; Metra, Marco; Stienen, Susan; Lombardi, Carlo; Tijssen, Jan G; Kok, Wouter E

2015-09-01

Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Type B Drum packages

International Nuclear Information System (INIS)

Edwards, W.S.

1995-11-01

The Type B Drum package is a container in which a single drum containing Type B quantities of radioactive material will be packaged for shipment. The Type B Drum containers are being developed to fill a void in the packaging and transportation capabilities of the US Department of Energy (DOE), as no double containment packaging for single drums of Type B radioactive material is currently available. Several multiple-drum containers and shielded casks presently exist. However, the size and weight of these containers present multiple operational challenges for single-drum shipments. The Type B Drum containers will offer one unshielded version and, if needed, two shielded versions, and will provide for the option of either single or double containment. The primary users of the Type B Drum container will be any organization with a need to ship single drums of Type B radioactive material. Those users include laboratories, waste retrieval facilities, emergency response teams, and small facilities

Predictive value of natriuretic peptides in dogs with mitral valve disease

DEFF Research Database (Denmark)

Tarnow, Inge; Olsen, Lisbeth Høier; Kvart, Clarence

2009-01-01

Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic...... peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs. Twenty seven CKCS and ten control dogs were re-examined 4 years after the initial examination...... and the status of the dogs 5 years after the initial examination was determined by telephone calls to the owner. All dogs were evaluated by clinical examination and echocardiography. CKCS with severe MR had higher NT-proANP and NT-proBNP compared to controls and CKCS with less severe MR. Dogs with clinical signs...

NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I

International Nuclear Information System (INIS)

Lacoste, J.; Cohen, L.; Hiscott, J.

1991-01-01

The effect of constitutive Tax expression on the interaction of NF-κ B with its recognition sequence and on NF-κ B-dependent gene expression was examined in T lymphoid Jurkat cell lines (19D and 9J) stably transformed with a Tax expression vector. Tax expressing T cell lines contained a constitutive level of NF-κ B binding activity, detectable by mobility shift assay and uv cross-linking using a palindromic NF-κ B probe homologous to the interferon beta PRDII site. In Jurkat and NC2.10 induction with phorbol esters resulted in the appearance of new DNA binding proteins of 85, 75, and 54 kDa, whereas in Tax expressing cells the 85-kDa protein and a 92-kDa DNA binding protein were constitutively induced. Expression of Tax protein in 19D and 9J resulted in transcription of the endogenous NF-kappa B-dependent granulocyte-macrophage colony stimulating factor gene and increased basal level expression of transfected NF-kappa B-regulated promoters. Nonetheless transcription of both the endogenous and the transfected gene was inducible by PMA treatment. Tax expression in Jurkat T cells may alter the stoichiometry of NF-kappa B DNA binding proteins and thus change the expression of NF-kappa B-regulated promoters

Type i CD20 antibodies recruit the B cell receptor for complement-dependent lysis of malignant B cells

DEFF Research Database (Denmark)

Engelberts, P. J.; Voorhorst, M.; Schuurman, J.

2016-01-01

. We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR- B cell lines. A direct relationship...... between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab')2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR- population. Importantly, OFA-F(ab')2 fragments were able to induce CDC ex vivo in malignant B cells...... isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC...

A-type and B-type lamins initiate layer assembly at distinct areas of the nuclear envelope in living cells

Energy Technology Data Exchange (ETDEWEB)

Furukawa, Kazuhiro, E-mail: furukawa@chem.sc.niigata-u.ac.jp [Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181 (Japan); Ishida, Kazuya; Tsunoyama, Taka-aki; Toda, Suguru; Osoda, Shinichi; Horigome, Tsuneyoshi [Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181 (Japan); Fisher, Paul A. [Department of Pharmacological Sciences, School of Medicine, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651 (United States); Sugiyama, Shin [Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602 (Japan)

2009-04-15

To investigate nuclear lamina re-assembly in vivo, Drosophila A-type and B-type lamins were artificially expressed in Drosophila lamin Dm{sub 0}null mutant brain cells. Both exogenous lamin C (A-type) and Dm{sub 0} (B-type) formed sub-layers at the nuclear periphery, and efficiently reverted the abnormal clustering of the NPC. Lamin C initially appeared where NPCs were clustered, and subsequently extended along the nuclear periphery accompanied by the recovery of the regular distribution of NPCs. In contrast, lamin Dm{sub 0} did not show association with the clustered NPCs during lamina formation and NPC spacing recovered only after completion of a closed lamin Dm{sub 0} layer. Further, when lamin Dm{sub 0} and C were both expressed, they did not co-polymerize, initiating layer formation in separate regions. Thus, A and B-type lamins reveal differing properties during lamina assembly, with A-type having the primary role in organizing NPC distribution. This previously unknown complexity in the assembly of the nuclear lamina could be the basis for intricate nuclear envelope functions.

Human T Cell Leukemia Virus Type I Tax-Induced IκB-ζ Modulates Tax-Dependent and Tax-Independent Gene Expression in T Cells

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Ryuichiro Kimura

2013-09-01

Full Text Available Human T cell leukemia virus type I (HTLV-I is the etiologic agent of adult T cell leukemia (ATL and various inflammatory disorders including HTLV-I-associated myelopathy/tropical spastic paraparesis. HTLV-I oncoprotein Tax is known to cause permanent activation of many cellular transcription factors including nuclear factor-κB (NF-κB, cyclic adenosine 3′,5′-monophosphate response element-binding protein, and activator protein 1 (AP-1. Here, we show that NF-κB-binding cofactor inhibitor of NF-κB-ζ (IκB-ζ is constitutively expressed in HTLV-I-infected T cell lines and ATL cells, and Tax transactivates the IκB-ζ gene, mainly through NF-κB. Microarray analysis of IκB-ζ-expressing uninfected T cells demonstrated that IκB-ζ induced the expression of NF-κB. and interferon-regulatory genes such as B cell CLL/lymphoma 3 (Bcl3, guanylate-binding protein 1, and signal transducer and activator of transcription 1. The transcriptional activation domain, nuclear localization signal, and NF-κB-binding domain of IκB-ζ were required for Bcl3 induction, and IκB-ζ synergistically enhanced Tax-induced Bcl3 transactivation in an NF-κB-dependent manner. Interestingly, IκB-ζ inhibited Tax-induced NF-κB, AP-1 activation, and HTLV-I transcription. Furthermore, IκB-ζ interacted with Tax in vitro and this interaction was also observed in an HTLV-I-transformed T cell line. These results suggest that IκB-ζ modulates Tax-dependent and Tax-independent gene transcription in T cells. The function of IκB-ζ may be of significance in ATL genesis and pathogenesis of HTLV-I-associated diseases.

Association of N-terminal pro-B-type natriuretic peptide with contrast-induced nephropathy and long-term outcomes in patients with chronic kidney disease and relative preserved left ventricular function.

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Liu, Yuan-hui; Liu, Yong; Zhou, Ying-ling; Yu, Dan-qing; He, Peng-cheng; Xie, Nian-jin; Li, Hua-long; Wei-Guo; Chen, Ji-yan; Tan, Ning

2015-04-01

The aim of the present article was to evaluate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with contrast-induced nephropathy (CIN) and long-term outcomes in patients with chronic kidney disease (CKD) and relative preserved left ventricular function (LVF) undergoing percutaneous coronary intervention (PCI). We prospectively enrolled 1203 consecutive patients with CKD and preserved LVF undergoing elective PCI. The primary end point was the development of CIN, defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dL, from baseline within 48 to 72 hours after contrast medium exposure. CIN incidence varied from 2.2% to 5.2%. Univariate logistic analysis showed that lg-NT-pro-BNP was significantly associated with CIN (odds ratio [OR] = 3.93, 95% confidence interval [CI], 2.22-6.97, P pro-BNP remained a significant predictor of CIN (OR = 3.30, 95% CI, 1.57-6.93, P = 0.002), even after adjusting for potential confounding risk factors. These results were confirmed by using other CIN criteria, which were defined as elevations of the SCr by 25% or 0.5 and 0.3 mg/dL from the baseline. The best cutoff value of lg-NT-pro-BNP for detecting CIN was 2.73 pg/mL (537 pg/mL) with 73.1% sensitivity and 70.0% specificity according to the receiver operating characteristic (ROC) analysis (C statistic = 0.754, 95% CI, 0.67-0.84, P pro-BNP ≥537 pg/mL (2.73 pg/mL, lg-NT-pro-BNP) was associated with an increased risk of all-cause mortality and composite end points during 2.5 years of follow-up. NT-pro-BNP ≥537 pg/mL is independently associated with an increased risk of CIN with different definitions and poor clinical outcomes in patients with CKD and relative preserved LVF undergoing PCI.

Multimarker Strategy for Heart Failure Prognostication. Value of Neurohormonal Biomarkers: Neprilysin vs NT-proBNP.

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Bayes-Genis, Antoni; Barallat, Jaume; Galán, Amparo; de Antonio, Marta; Domingo, Mar; Zamora, Elisabet; Gastelurrutia, Paloma; Vila, Joan; Peñafiel, Judith; Gálvez-Montón, Carolina; Lupón, Josep

2015-12-01

Neprilysin breaks down numerous vasoactive peptides. The soluble form of neprilysin, which was recently identified in heart failure, is associated with cardiovascular outcomes. Within a multibiomarker strategy, we directly compared soluble neprilysin and N-terminal pro-B-type natriuretic peptide as risk stratifiers in a real-life cohort of heart failure patients. Soluble neprilysin, N-terminal pro-B-type natriuretic peptide, ST2, and high-sensitivity troponin T levels were measured in 797 consecutive ambulatory heart failure patients followed up for 4.7 years. Comprehensive multivariable analyses and soluble neprilysin vs N-terminal pro-B-type natriuretic peptide head-to-head assessments of performance were performed. A primary composite endpoint included cardiovascular death or heart failure hospitalization. A secondary endpoint explored cardiovascular death alone. Median soluble neprilysin and N-terminal pro-B-type natriuretic peptide concentrations were 0.64ng/mL and 1187 ng/L, respectively. Both biomarkers significantly correlated with age (P<.001) and ST2 (P<.001), but only N-terminal pro-B-type natriuretic peptide significantly correlated with estimated glomerular filtration rate (P<.001), body mass index (P<.001), left ventricular ejection fraction (P=.02) and high-sensitivity troponin T (P<.001). In multivariable Cox regression analyses, soluble neprilysin remained independently associated with the composite endpoint (hazard ratio=1.14; 95% confidence interval, 1.02-1.27; P=.03) and cardiovascular death (hazard ratio=1.15; 95% confidence interval, 1.01-1.31; P=.04), but N-terminal pro-B-type natriuretic peptide did not. The head-to-head soluble neprilysin vs N-terminal pro-B-type natriuretic peptide comparison showed good calibration and similar discrimination and reclassification for both neurohormonal biomarkers, but only soluble neprilysin improved overall goodness-of-fit. When added to a multimarker strategy, soluble neprilysin remained an independent

Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

Science.gov (United States)

Ishikura, Fuminobu; Beppu, Shintaro; Asanuma, Toshihiko; Seward, James B; Khandheria, Bijoy K

2007-12-01

Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells.

Science.gov (United States)

Komlósi, Zsolt I; Kovács, Nóra; van de Veen, Willem; Kirsch, Anna Isabella; Fahrner, Heinz Benedikt; Wawrzyniak, Marcin; Rebane, Ana; Stanic, Barbara; Palomares, Oscar; Rückert, Beate; Menz, Günter; Akdis, Mübeccel; Losonczy, György; Akdis, Cezmi A

2017-09-20

Type 3 innate lymphoid cells (ILC3s) are involved in maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified. We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects. A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L + ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients. Human CD40L + ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The oxidation of alkylaryl sulfides and benzo[b]thiophenes by Escherichia coli cells expressing wild-type and engineered styrene monooxygenase from Pseudomonas putida CA-3.

Science.gov (United States)

Nikodinovic-Runic, Jasmina; Coulombel, Lydie; Francuski, Djordje; Sharma, Narain D; Boyd, Derek R; Ferrall, Rory Moore O; O'Connor, Kevin E

2013-06-01

Nine different sulfur-containing compounds were biotransformed to the corresponding sulfoxides by Escherichia coli Bl21(DE3) cells expressing styrene monooxygenase (SMO) from Pseudomonas putida CA-3. Thioanisole was consumed at 83.3 μmoles min(-1) g cell dry weight(-1) resulting mainly in the formation of R-thioanisole sulfoxide with an enantiomeric excess (ee) value of 45 %. The rate of 2-methyl-, 2-chloro- and 2-bromo-thioanisole consumption was 2-fold lower than that of thioanisole. Surprisingly, the 2-methylthioanisole sulfoxide product had the opposite (S) configuration to that of the other 2-substituted thioanisole derivatives and had a higher ee value (84 %). The rate of oxidation of 4-substituted thioanisoles was higher than the corresponding 2-substituted substrates but the ee values of the products were consistently lower (10-23 %). The rate of benzo[b]thiophene and 2-methylbenzo[b]thiophene sulfoxidation was approximately 10-fold lower than that of thioanisole. The ee value of the benzo[b]thiophene sulfoxide could not be determined as the product racemized rapidly. E. coli cells expressing an engineered SMO (SMOeng R3-11) oxidised 2-substituted thioanisoles between 1.8- and 2.8-fold faster compared to cells expressing the wild-type enzyme. SMOeng R3-11 oxidised benzo[b]thiophene and 2-methylbenzo[b]thiophene 10.1 and 5.6 times faster that the wild-type enzyme. The stereospecificity of the reaction catalysed by SMOeng was unchanged from that of the wild type. Using the X-ray crystal structure of the P. putida S12 SMO, it was evident that the entrance of substrates into the SMO active site is limited by the binding pocket bottleneck formed by the side chains of Val-211 and Asn-46 carboxyamide group.

Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.

Science.gov (United States)

Miyanishi, Hiroshi; Okubo, Kataaki; Nobata, Shigenori; Takei, Yoshio

2013-01-01

Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.

Natriuretic Peptides as Biomarkers for Congestive States: The Cardiorenal Divergence

Directory of Open Access Journals (Sweden)

Abhilash Koratala

2017-01-01

Full Text Available Congestion represents the primary reason for hospitalization of patients with heart failure and is associated with adverse outcomes. Fluid overload has been shown to be inadequately addressed in a significant subset of these patients in part due to lack of robust, reliable, and readily available biomarkers for objective assessment and monitoring of therapy. Natriuretic peptides have long been used in this setting, often in conjunction with other assessment tools such as imaging studies. Patients presenting with concomitant cardiac and renal dysfunction represent a unique population with regard to congestion in that the interactions between the heart and the kidney can affect the utility and performance of biomarkers of fluid overload. Herein, we provide an overview of the currently available evidence on the utility of natriuretic peptides in these patients and discuss the clinical conundrum associated with their use in the setting of renal dysfunction. We highlight the potential divergence in the role of natriuretic peptides for assessment of volume status in a subset of patients with renal dysfunction who receive renal replacement therapy and call for future research to elucidate the utility of the biomarkers in this setting.

Regulated gene expression in cultured type II cells of adult human lung.

Science.gov (United States)

Ballard, Philip L; Lee, Jae W; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R; Fischer, Horst; Illek, Beate; Gonzales, Linda W; Kolla, Venkatadri; Matthay, Michael A

2010-07-01

Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at approximately 95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days on collagen-coated dishes with or without DCI for the final 3 days. In freshly isolated cells, highly expressed genes included SFTPA/B/C, SCGB1A, IL8, CXCL2, and SFN in addition to ubiquitously expressed genes. Transcript abundance was correlated between fetal and adult cells (r = 0.88), with a subset of 187 genes primarily related to inflammation and immunity that were expressed >10-fold higher in adult cells. During control culture, expression increased for 8.1% of expressed genes and decreased for approximately 4% including 118 immune response and 10 surfactant-related genes. DCI treatment promoted lamellar body production and increased expression of approximately 3% of probed genes by > or =1.5-fold; 40% of these were also induced in fetal cells. Highly induced genes (> or =10-fold) included PGC, ZBTB16, DUOX1, PLUNC, CIT, and CRTAC1. Twenty-five induced genes, including six genes related to surfactant (SFTPA/B/C, PGC, CEBPD, and ADFP), also had decreased expression during control culture and thus are candidates for hormonal regulation in vivo. Our results further define the adult human type II cell molecular phenotype and demonstrate that a subset of genes remains hormone responsive in cultured adult cells.

Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

Science.gov (United States)

Woitek, Felix; Zentilin, Lorena; Hoffman, Nicholas E; Powers, Jeffery C; Ottiger, Isabel; Parikh, Suraj; Kulczycki, Anna M; Hurst, Marykathryn; Ring, Nadja; Wang, Tao; Shaikh, Farah; Gross, Polina; Singh, Harinder; Kolpakov, Mikhail A; Linke, Axel; Houser, Steven R; Rizzo, Victor; Sabri, Abdelkarim; Madesh, Muniswamy; Giacca, Mauro; Recchia, Fabio A

2015-07-14

Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study.

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Gergei, Ingrid; Krämer, Bernhard K; Scharnagl, Hubert; Stojakovic, Tatjana; März, Winfried; Mondorf, Ulrich

The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF). We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP). Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years). Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF. The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF. Big-ET-1improves risk stratification in patients referred for coronary angiography.

Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes.

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Iida, Masato; Yamamoto, Mitsuru; Ishiguro, Yuko S; Yamazaki, Masatoshi; Ueda, Norihiro; Honjo, Haruo; Kamiya, Kaichirou

2014-01-01

Urinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions. We studied hypertensive patients with early prediabetes (HbA1c 110, n=18), those with prediabetes (HbA1c 5.7-6.4, n=98), and those with diabetes (HbA1c>6.5 or on diabetes medications, n=92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e'). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e'≥15, or E/e'=9-14 accompanied by left atrial volume/BSA≥32ml/mm(2). Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c. Urinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes. In hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP. Copyright © 2014 Elsevier Inc. All rights reserved.

Human T Cell Leukemia Virus Type I Tax-Induced IκB-ζ Modulates Tax-Dependent and Tax-Independent Gene Expression in T Cells1

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Kimura, Ryuichiro; Senba, Masachika; Cutler, Samuel J; Ralph, Stephen J; Xiao, Gutian; Mori, Naoki

2013-01-01

Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia (ATL) and various inflammatory disorders including HTLV-I-associated myelopathy/tropical spastic paraparesis. HTLV-I oncoprotein Tax is known to cause permanent activation of many cellular transcription factors including nuclear factor-κB (NF-κB), cyclic adenosine 3′,5′-monophosphate response element-binding protein, and activator protein 1 (AP-1). Here, we show that NF-κB-binding cofactor inhibitor of NF-κB-ζ (IκB-ζ) is constitutively expressed in HTLV-I-infected T cell lines and ATL cells, and Tax transactivates the IκB-ζ gene, mainly through NF-κB. Microarray analysis of IκB-ζ-expressing uninfected T cells demonstrated that IκB-ζ induced the expression of NF-κB. and interferon-regulatory genes such as B cell CLL/lymphoma 3 (Bcl3), guanylate-binding protein 1, and signal transducer and activator of transcription 1. The transcriptional activation domain, nuclear localization signal, and NF-κB-binding domain of IκB-ζ were required for Bcl3 induction, and IκB-ζ synergistically enhanced Tax-induced Bcl3 transactivation in an NF-κB-dependent manner. Interestingly, IκB-ζ inhibited Tax-induced NF-κB, AP-1 activation, and HTLV-I transcription. Furthermore, IκB-ζ interacted with Tax in vitro and this interaction was also observed in an HTLV-I-transformed T cell line. These results suggest that IκB-ζ modulates Tax-dependent and Tax-independent gene transcription in T cells. The function of IκB-ζ may be of significance in ATL genesis and pathogenesis of HTLV-I-associated diseases. PMID:24027435

Practical application of natriuretic peptides in paediatric cardiology

DEFF Research Database (Denmark)

Smith, Julie; Goetze, Jens Peter; B. Andersen, Claus

2010-01-01

It is still uncertain if cardiac natriuretic peptides are useful biomarkers in paediatric cardiology. In this review we identify four clinical scenarios in paediatric cardiology, where clinical decision-making can be difficult, and where we feel the paediatric cardiologists need additional...

Distinctive expression pattern of OCT4 variants in different types of breast cancer.

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Soheili, Saamaaneh; Asadi, Malek Hossein; Farsinejad, Alireza

2017-01-01

OCT4 is a key regulator of self-renewal and pluripotency in embryonic stem cells which can potentially encode three spliced variants designated OCT4A, OCT4B and OCT4B1. Based on cancer stem cell concept, it is suggested that the stemness factors misexpressed in cancer cells and potentially is involved in tumorigenesis. Accordingly, in this study, we investigated the potential expression of OCT4 variants in breast cancer tissues. A total of 94 tumoral and peritumoral breast specimens were evaluated with respect to the expression of OCT4 variants using quantitative RT-PCR and immunohistochemical (IHC) analysis. We detected the expression of OCT4 variants in breast tumor tissues with no or very low levels of expression in peritumoral samples of the same patients. While OCT4B was highly expressed in lobular type of breast cancer, OCT4A and OCTB1 variants are highly expressed in low grade (I and II) ductal tumors. Furthermore, the results of this study revealed a considerable association between the expression level of OCT4 variants and the expression of ER, PR, Her2 and P53 factors. All data demonstrated a distinctive expression pattern of OCT4 spliced variants in different types of breast cancer and provide further evidence for the involvement of embryonic genes in carcinogenesis.

Comparative transcriptome analysis on the alteration of gene expression in ayu (Plecoglossus altivelis larvae associated with salinity change

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Xin-Jiang LU

2016-05-01

Full Text Available Ayu (Plecoglossus altivelis fish, which are an amphidromous species distributed in East Asia, live in brackish water (BW during their larval stage and in fresh water (FW during their adult stage. In this study, we found that FW-acclimated ayu larvae exhibited a slower growth ratio compared with that of BW-acclimated larvae. However, the mechanism underlying FW acclimation on growth suppression is poorly known. We employed transcriptome analysis to investigate the differential gene expression of FW acclimation by RNA sequencing. We identified 158 upregulated and 139 downregulated transcripts in FW-acclimated ayu larvae compared with that in BW-acclimated larvae. As determined by Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway mapping, functional annotation of the genes covered diverse biological functions and processes, and included neuroendocrinology, osmotic regulation, energy metabolism, and the cytoskeleton. Transcriptional expression of several differentially expressed genes in response to FW acclimation was further confirmed by real-time quantitative PCR. In accordance with transcriptome analysis, iodothyronine deiodinase (ID, pro-opiomelanocortin (POMC, betaine-homocysteine S-methyltransferase 1(BHMT, fructose-bisphosphate aldolase B (aldolase B, tyrosine aminotransferase (TAT, and Na+-K+ ATPase (NKA were upregulated after FW acclimation. Furthermore, the mRNA expressions of b-type natriuretic peptide (BNP and transgelin were downregulated after FW acclimation. Our data indicate that FW acclimation reduced the growth rate of ayu larvae, which might result from the expression alteration of genes related to endocrine hormones, energy metabolism, and direct osmoregulation.

Comparative transcriptome analysis on the alteration of gene expression in ayu (Plecoglossus altivelis) larvae associated with salinity change.

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Lu, Xin-Jiang; Zhang, Hao; Yang, Guan-Jun; Li, Ming-Yun; Chen, Jiong

2016-05-18

Ayu (Plecoglossus altivelis) fish, which are an amphidromous species distributed in East Asia, live in brackish water (BW) during their larval stage and in fresh water (FW) during their adult stage. In this study, we found that FW-acclimated ayu larvae exhibited a slower growth ratio compared with that of BW-acclimated larvae. However, the mechanism underlying FW acclimation on growth suppression is poorly known. We employed transcriptome analysis to investigate the differential gene expression of FW acclimation by RNA sequencing. We identified 158 upregulated and 139 downregulated transcripts in FW-acclimated ayu larvae compared with that in BW-acclimated larvae. As determined by Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway mapping, functional annotation of the genes covered diverse biological functions and processes, and included neuroendocrinology, osmotic regulation, energy metabolism, and the cytoskeleton. Transcriptional expression of several differentially expressed genes in response to FW acclimation was further confirmed by real-time quantitative PCR. In accordance with transcriptome analysis, iodothyronine deiodinase (ID), pro-opiomelanocortin (POMC), betaine-homocysteine S-methyltransferase 1(BHMT), fructose-bisphosphate aldolase B (aldolase B), tyrosine aminotransferase (TAT), and Na(+)-K(+) ATPase (NKA) were upregulated after FW acclimation. Furthermore, the mRNA expressions of b-type natriuretic peptide (BNP) and transgelin were downregulated after FW acclimation. Our data indicate that FW acclimation reduced the growth rate of ayu larvae, which might result from the expression alteration of genes related to endocrine hormones, energy metabolism, and direct osmoregulation.

Scavenger Receptor Class B, Type I, a CD36 Related Protein in Macrobrachium nipponense: Characterization, RNA Interference, and Expression Analysis with Different Dietary Lipid Sources

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Zhili Ding

2016-01-01

Full Text Available The scavenger receptor class B, type I (SR-BI, is a member of the CD36 superfamily comprising transmembrane proteins involved in mammalian and fish lipid homeostasis regulation. We hypothesize that this receptor plays an important role in Macrobrachium nipponense lipid metabolism. However, little attention has been paid to SR-BI in commercial crustaceans. In the present study, we report a cDNA encoding M. nipponense scavenger receptor class B, type I (designated as MnSR-BI, obtained from a hepatopancreas cDNA library. The complete MnSR-BI coding sequence was 1545 bp, encoding 514 amino acid peptides. The MnSR-BI primary structure consisted of a CD36 domain that contained two transmembrane regions at the N- and C-terminals of the protein. SR-BI mRNA expression was specifically detected in muscle, gill, ovum, intestine, hepatopancreas, stomach, and ovary tissues. Furthermore, its expression in the hepatopancreas was regulated by dietary lipid sources, with prawns fed soybean and linseed oils exhibiting higher expression levels. RNAi-based SR-BI silencing resulted in the suppression of its expression in the hepatopancreas and variation in the expression of lipid metabolism-related genes. This is the first report of SR-BI in freshwater prawns and provides the basis for further studies on SR-BI in crustaceans.

Expression pattern and function of tyrosine receptor kinase B isoforms in rat mesenteric arterial smooth muscle cells

International Nuclear Information System (INIS)

Otani, Kosuke; Okada, Muneyoshi; Yamawaki, Hideyuki

2015-01-01

Tyrosine receptor kinaseB (TrkB) is a high affinity receptor for brain-derived neurotrophic factor (BDNF). TrkB isoforms involve full length TrkB (TrkB FL) and truncated TrkB type1 (TrkB T1) and type 2 (TrkB T2) in rats. The aim of present study was to explore their expression pattern and function in mesenteric arterial smooth muscle cells (MASMCs). The expression of TrkB isoform protein and mRNA was examined by Western blotting, immunofluorescence and quantitative RT-PCR analyses. Cell proliferation was measured by a bromodeoxyuridine (BrdU) incorporation assay. Cell migration was measured by a Boyden chamber assay. Cell morphology was observed with a phase-contrast microscope. Protein and mRNA expression of BDNF and TrkB isoforms was confirmed in MASMCs. Expression level of TrkB FL was less, while that of TrkB T1 was the highest in MASMCs. Although BDNF increased phosphorylation of ERK, it had no influence on migration and proliferation of MASMCs. TrkB T1 gene knockdown by a RNA interference induced morphological changes and reduced expression level of α-smooth muscle actin (α-SMA) in MASMCs. Similar morphological changes and reduced α-SMA expression were induced in MASMCs by a Rho kinase inhibitor, Y-27632. In conclusion, we for the first time demonstrate that TrkB T1 expressed highly in MASMCs contributes to maintain normal cell morphology possibly via regulation of Rho activity. This study firstly defined expression level of TrkB isoforms and partly revealed their functions in peripheral vascular cells. - Highlights: • BDNF-TrkB axis mediates neurogenesis, growth, differentiation and survival. • Expression pattern and function of TrkB in vascular smooth muscle remain unclear. • Expression of TrkB FL is low, while that of TrkB T1 is the highest. • TrkB T1 contributes to maintain normal morphology possibly via activating Rho.

Expression pattern and function of tyrosine receptor kinase B isoforms in rat mesenteric arterial smooth muscle cells

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Otani, Kosuke; Okada, Muneyoshi; Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp

2015-11-27

Tyrosine receptor kinaseB (TrkB) is a high affinity receptor for brain-derived neurotrophic factor (BDNF). TrkB isoforms involve full length TrkB (TrkB FL) and truncated TrkB type1 (TrkB T1) and type 2 (TrkB T2) in rats. The aim of present study was to explore their expression pattern and function in mesenteric arterial smooth muscle cells (MASMCs). The expression of TrkB isoform protein and mRNA was examined by Western blotting, immunofluorescence and quantitative RT-PCR analyses. Cell proliferation was measured by a bromodeoxyuridine (BrdU) incorporation assay. Cell migration was measured by a Boyden chamber assay. Cell morphology was observed with a phase-contrast microscope. Protein and mRNA expression of BDNF and TrkB isoforms was confirmed in MASMCs. Expression level of TrkB FL was less, while that of TrkB T1 was the highest in MASMCs. Although BDNF increased phosphorylation of ERK, it had no influence on migration and proliferation of MASMCs. TrkB T1 gene knockdown by a RNA interference induced morphological changes and reduced expression level of α-smooth muscle actin (α-SMA) in MASMCs. Similar morphological changes and reduced α-SMA expression were induced in MASMCs by a Rho kinase inhibitor, Y-27632. In conclusion, we for the first time demonstrate that TrkB T1 expressed highly in MASMCs contributes to maintain normal cell morphology possibly via regulation of Rho activity. This study firstly defined expression level of TrkB isoforms and partly revealed their functions in peripheral vascular cells. - Highlights: • BDNF-TrkB axis mediates neurogenesis, growth, differentiation and survival. • Expression pattern and function of TrkB in vascular smooth muscle remain unclear. • Expression of TrkB FL is low, while that of TrkB T1 is the highest. • TrkB T1 contributes to maintain normal morphology possibly via activating Rho.

Relationship between natriuretic peptides and inflammation: proteomic evidence obtained during acute cellular cardiac allograft rejection in humans.

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Meirovich, Yael F; Veinot, John P; de Bold, Mercedes L Kuroski; Haddad, Haissam; Davies, Ross A; Masters, Roy G; Hendry, Paul J; de Bold, Adolfo J

2008-01-01

Cardiac natriuretic peptides (NPs) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are polypeptide hormones secreted by the heart. Previously, we found that BNP, but not ANF, plasma levels may increase during an acute cellular cardiac allograft rejection episode. In vitro, the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) produced a selective increase of BNP gene expression and secretion. Other pro-inflammatory cytokines had no such effects. We identified cytokines associated with the selective upregulation of BNP during cardiac allograft rejection using a proteomics approach to measure 120 cytokines and related substances in the plasma of 16 transplant patients before, during and after an acute rejection episode. The values obtained were correlated with BNP plasma levels. Cytokines identified as being significantly related to BNP plasma levels were tested in neonatal rat ventricular cardiocytes in culture for their ability to selectively promote BNP secretion. The signaling pathway related to this phenomenon was pharmacologically characterized. Regulated-on-activation, normal T-expressed and secreted (RANTES), neutrophil-activating protein-2 (NAP-2) and insulin growth factor binding protein-1 (IGFBP-1) had significant correlations with BNP plasma levels during Grade 3A (Grade 2 revised [2R]) or above rejection as diagnosed by endomyocardial biopsy score according to the International Society for Heart and Lung Transplantation (ISHLT) grading system. In rat neonatal ventricular cardiocyte cultures, IGFBP-1 and RANTES were capable of promoting BNP, but not ANF secretion, as observed in rejecting patients. The BNP-promoting secretion activity of the identified cytokines was abolished by SB203580, a specific p38 MAP kinase inhibitor. This work shows that cytokines other than pro-inflammatory cytokines correlate with BNP plasma levels observed during acute cardiac allograft rejection, and that

Differential spatial expression of A- and B-type CDKs, and distribution of auxins and cytokinins in the open transverse root apical meristem of Cucurbita maxima.

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Chiappetta, Adriana; Bruno, Leonardo; Salimonti, Amelia; Muto, Antonella; Jones, Jessica; Rogers, Hilary J; Francis, Dennis; Bitonti, Maria Beatrice

2011-05-01

Aside from those on Arabidopsis, very few studies have focused on spatial expression of cyclin-dependent kinases (CDKs) in root apical meristems (RAMs), and, indeed, none has been undertaken for open meristems. The extent of interfacing between cell cycle genes and plant growth regulators is also an increasingly important issue in plant cell cycle studies. Here spatial expression/localization of an A-type and B-type CDK, auxin and cytokinins are reported in relation to the hitherto unexplored anatomy of RAMs of Cucurbita maxima. Median longitudinal sections were cut from 1-cm-long primary root tips of C. maxima. Full-length A-type CDKs and a B-type CDK were cloned from C. maxima using degenerate primers, probes of which were localized on sections of RAMs using in situ hybridization. Isopentenyladenine (iPA), trans-zeatin (t-Z) and indole-3yl-acetic acid (IAA) were identified on sections by immunolocalization. The C. cucurbita RAM conformed to an open transverse (OT) meristem typified by an absence of a clear boundary between the eumeristem and root cap columella, but with a distinctive longitudinally thickened epidermis. Cucma;CDKA;1 expression was detected strongly in the longitudinally thickened epidermis, a tissue with mitotic competence that contributes cells radially to the root cap of OT meristems. Cucma;CDKB2 was expressed mainly in proliferative regions of the RAM and in lateral root primordia. iPA and t-Z were mainly distributed in differentiated cells whilst IAA was distributed more uniformly in all tissues of the RAM. Cucma;CDKA;1 was expressed most strongly in cells that have proliferative competence whereas Cucma;CDKB2 was confined mainly to mitotic cells. iPA and t-Z marked differentiated cells in the RAM, consistent with the known effect of cytokinins in promoting differentiation in root systems. iPA/t-Z were distributed in a converse pattern to Cucma;CDKB2 expression whereas IAA was detected in most cells in the RAM regardless of their proliferative

Clinical significance of detection of plasma natriuretic peptide in the diagnosis of patients with heart failure

International Nuclear Information System (INIS)

Song Chunli; Liu Haihong; Zhao Ning; Li Jie; Huang Jianmin

2009-01-01

To explore the clinical significance of plasma natriuretic peptide in the diagnosis of patients with heart failure (HF), the plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), NT-pro brain natriuretic peptide (NT-proBNP) levels in 129 patients with heart failure and 30 healthy controls were detected by RIA and ELISA. The results showed that the plasma ANP, BNP, NT-proBNP levels in patients with heart failure were significantly higher than the healthy controls. As the cardiac function deteriorated from NYHA I to IV, the BNP and NT-proBNP levels increased consecutively with significant differences from each other. There was a negative correlation between the plasma ANP and NT-proBNP levels and LVEF. The determination of plasma ANP, BNP and NT-proBNP levels in patients with HF were helpful to the study of the severity and diagnosis of disease. (authors)

Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A.

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Disertori, Marcello; Quintarelli, Silvia; Grasso, Maurizia; Pilotto, Andrea; Narula, Nupoor; Favalli, Valentina; Canclini, Camilla; Diegoli, Marta; Mazzola, Silvia; Marini, Massimiliano; Del Greco, Maurizio; Bonmassari, Roberto; Masè, Michela; Ravelli, Flavia; Specchia, Claudia; Arbustini, Eloisa

2013-02-01

Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy. We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide. Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.

Impaired Integrin-mediated Adhesion and Signaling in Fibroblasts Expressing a Dominant-negative Mutant PTP1B

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Arregui, Carlos O.; Balsamo, Janne; Lilien, Jack

1998-01-01

To investigate the role of nonreceptor protein tyrosine phosphatase 1B (PTP1B) in β1-integrin– mediated adhesion and signaling, we transfected mouse L cells with normal and catalytically inactive forms of the phosphatase. Parental cells and cells expressing the wild-type or mutant PTP1B were assayed for (a) adhesion, (b) spreading, (c) presence of focal adhesions and stress fibers, and (d) tyrosine phosphorylation. Parental cells and cells expressing wild-type PTP1B show similar morphology, are able to attach and spread on fibronectin, and form focal adhesions and stress fibers. In contrast, cells expressing the inactive PTP1B have a spindle-shaped morphology, reduced adhesion and spreading on fibronectin, and almost a complete absence of focal adhesions and stress fibers. Attachment to fibronectin induces tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin in parental cells and cells transfected with the wild-type PTP1B, while in cells transfected with the mutant PTP1B, such induction is not observed. Additionally, in cells expressing the mutant PTP1B, tyrosine phosphorylation of Src is enhanced and activity is reduced. Lysophosphatidic acid temporarily reverses the effects of the mutant PTP1B, suggesting the existence of a signaling pathway triggering focal adhesion assembly that bypasses the need for active PTP1B. PTP1B coimmunoprecipitates with β1-integrin from nonionic detergent extracts and colocalizes with vinculin and the ends of actin stress fibers in focal adhesions. Our data suggest that PTP1B is a critical regulatory component of integrin signaling pathways, which is essential for adhesion, spreading, and formation of focal adhesions. PMID:9813103

Plasma natriuretic peptides in children and adolescents with obstructive sleep apnoea and their changes following intervention

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Albert Martin Li

2014-03-01

Full Text Available Objective: This study aimed to evaluate circulating natriuretic peptides (NP concentration in obese and non-obese children and adolescents with and without OSA, and their levels following OSA treatment.Methods: Subjects with habitual snoring and symptoms suggestive of OSA were recruited. They underwent physical examination and overnight polysomnography (PSG. OSA was diagnosed if obstructive apnea hypopnea index (OAHI ≥1/h. Fasting serum atrial natriuretic peptide (ANP and brain natriuretic peptide (BNP were taken after overnight PSG. The subjects were divided into obese, non-obese, with and without OSA groups for comparisons.Results: 114 children (77 were boys with a median (IQR age of 10.8 (8.3-12.7 years (range: 2.4-11.8 years were recruited. Sixty-eight subjects were found to have OSA. Natriuretic peptide levels did not differ between subjects with and without OSA in both obese and non-obese groups. . Stepwise multiple linear regressions revealed that body mass index (BMI z-score was the only independent factor associated with NP concentrations. Fifteen children with moderate-to-severe OSA (OAHI >5/h underwent treatment and there were no significant changes in both ANP and BNP levels after intervention.Conclusion: BMI rather than OSA was the main determinant of natriuretic peptide levels in school-aged children and adolescents.

Expressão imuno-histoquímica de c-erb-B2 e p53 em carcinomas gástricos Imunohistochemical expression of c-erb-B2 and p53 in gastric carcinomas

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Maria Dirlei F. S. Begnami

2005-08-01

entire circunference of the cell membrane was stained in > 10% of the tumor cells. RESULTS: Overall expression of p53 and c-erb-B2 was observed in 30% and 12% of gastric carcinomas cases, respectively. Relationship with intestinal type of gastric carcinomas and expression of c-erb-B2 was shown (p < 0.001, and expression of p53 was observed in tumors larger than 5cm (p = 0.003. There was not significant difference in survival curves of patients with gastric cancer in relation to the expression of these markers. CONCLUSION: Intestinal type of gastric carcinomas in our country are more frequently positive for c-erb-B2 than diffuse type. The expression of p53 is associated with tumor size. The TMA is a valid and efficient way to study immunohistochemical markers, having a high correlation with the full section.

Optimization of culture conditions to improve the expression level of beta1–epsilon toxin of Clostridium perfringens type B in Escherichia coli

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Chuwen Lin

2016-03-01

Full Text Available The detoxified beta1–epsilon (β1–ϵ toxin protein of Clostridium perfringens type B provides protection from C. perfringens types B, C and D infections. Acetate is the primary by-product from the cell growth and expression of β1–ϵ protein. In the present study, the effects of pH and dissolved oxygen (DO on the expression of β1--ϵ protein were investigated. Two-stage pH and DO control strategies were developed for the expression of β1–ϵ protein. The obtained results indicated that higher cell density and concentration of β1--ϵ protein, and lower accumulation of acetate were obtained when pH was maintained at a constant level of 6.5 (0–6 h and 7.0 (6–16 h, and the DO level was maintained at 60% (0–6 h and 30% (6–16 h. Furthermore, the impact of intermittent, DO feedback, pH feedback and glucose-stat feeding on the expression of β1–ϵ protein were studied. By using the DO feedback feeding, combined with the stage control of pH (6.5 for 0–6 h, 7.0 for 6–16 h and DO (60% for 0–6 h, 30% for 6–16 h, the highest cell density of 2.045 (absorbance at 600 nm and a β1–ϵ protein concentration of 63.24 mg/L were obtained, and the accumulation of acetate decreased to 0.872 g/L.

Differences in Natriuretic Peptide Levels by Race/Ethnicity (From the Multi-Ethnic Study of Atherosclerosis).

Science.gov (United States)

Gupta, Deepak K; Daniels, Lori B; Cheng, Susan; deFilippi, Christopher R; Criqui, Michael H; Maisel, Alan S; Lima, Joao A; Bahrami, Hossein; Greenland, Philip; Cushman, Mary; Tracy, Russell; Siscovick, David; Bertoni, Alain G; Cannone, Valentina; Burnett, John C; Carr, John Jeffrey; Wang, Thomas J

2017-09-15

Natriuretic peptides (NP) are cardiac-derived hormones with favorable cardiometabolic actions. Low NP levels are associated with increased risks of hypertension and diabetes mellitus, conditions with variable prevalence by race and ethnicity. Heritable factors underlie a significant proportion of the interindividual variation in NP concentrations, but the specific influences of race and ancestry are unknown. In 5597 individuals (40% white, 24% black, 23% Hispanic, and 13% Chinese) without prevalent cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis, multivariable linear regression and restricted cubic splines were used to estimate differences in serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels according to, ethnicity, and ancestry. Ancestry was determined using genetic ancestry informative markers. NT-proBNP concentrations differed significantly by race and ethnicity (black, median 43 pg/ml [interquartile range 17 to 94], Chinese 43 [17 to 90], Hispanic 53 [23 to 107], white 68 [34 to 136]; p = 0.0001). In multivariable models, NT-proBNP was 44% lower (95% confidence interval -48 to -40) in black and 46% lower (-50 to -41) in Chinese, compared with white individuals. Hispanic individuals had intermediate concentrations. Self-identified blacks and Hispanics were the most genetically admixed. Among self-identified black individuals, a 20% increase in genetic European ancestry was associated with 12% higher (1% to 23%) NT-proBNP. Among Hispanic individuals, genetic European and African ancestry were positively and negatively associated with NT-proBNP levels, respectively. In conclusion, NT-proBNP levels differ according to race and ethnicity, with the lowest concentrations in black and Chinese individuals. Racial and ethnic differences in NT-proBNP may have a genetic basis, with European and African ancestry associated with higher and lower NT-proBNP concentrations, respectively. Copyright © 2017 Elsevier Inc. All

Containment analysis for Type B packages used to transport various contents

International Nuclear Information System (INIS)

Anderson, B.L.; Carlson, R.W.; Fischer, L.E.

1996-11-01

This report presents sample containment analyses and examples of leakage rate calculations for Type B packages used to transport various contents. Samples of acceptance standard leakage rates are developed for specific contents types at normal transport conditions and at hypothetical accident conditions. The leakage rates are expressed as allowable standard leakage rates. The type of contents considered include: (1) powders, (2) liquids, (3) irradiated fuel rods, (4) gases, and (5) solids

Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas.

Science.gov (United States)

Menguy, Sarah; Frison, Eric; Prochazkova-Carlotti, Martina; Dalle, Stephane; Dereure, Olivier; Boulinguez, Serge; Dalac, Sophie; Machet, Laurent; Ram-Wolff, Caroline; Verneuil, Laurence; Gros, Audrey; Vergier, Béatrice; Beylot-Barry, Marie; Merlio, Jean-Philippe; Pham-Ledard, Anne

2018-03-26

In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with

Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice.

Science.gov (United States)

Grant, Marianne K O; Seelig, Davis M; Sharkey, Leslie C; Zordoky, Beshay N

2017-01-01

There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known. Therefore, in the present study, we determined the effect of acute DOX exposure on the expression of CYP genes in the hearts of both male and female C57Bl/6 mice. Acute DOX cardiotoxicity was induced by a single intraperitoneal injection of 20 mg/kg DOX in male and female adult C57Bl/6 mice. Cardiac function was assessed 5 days after DOX exposure by trans-thoracic echocardiography. Mice were euthanized 1 day or 6 days after DOX or saline injection. Thereafter, the hearts were harvested and weighed. Heart sections were evaluated for pathological lesions. Total RNA was extracted and expression of natriuretic peptides, inflammatory and apoptotic markers, and CYP genes was measured by real-time PCR. Adult female C57Bl/6 mice were protected from acute DOX-induced cardiotoxicity as they show milder pathological lesions, less inflammation, and faster recovery from DOX-induced apoptosis and DOX-mediated inhibition of beta-type natriuretic peptide. Acute DOX exposure altered the gene expression of multiple CYP genes in a sex-dependent manner. In 24 h, DOX exposure caused male-specific induction of Cyp1b1 and female-specific induction of Cyp2c29 and Cyp2e1. Acute DOX exposure causes sex-dependent alteration of cardiac CYP gene expression. Since cardiac CYP enzymes metabolize several endogenous compounds to biologically active metabolites, sex-dependent alteration of CYP genes may play a role in the sexual dimorphism of acute DOX

Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging.

Science.gov (United States)

Sangaralingham, S Jeson; Heublein, Denise M; Grande, Joseph P; Cataliotti, Alessandro; Rule, Andrew D; McKie, Paul M; Martin, Fernando L; Burnett, John C

2011-11-01

Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.

Natriuretic peptides: prediction of cardiovascular disease in the general population and high risk populations

DEFF Research Database (Denmark)

Hildebrandt, Per

2009-01-01

(General Practitioner) setting as in the acute setting. Supporting this use is a very strong prognostic value of the natriuretic peptides. This has been shown in as well heart failure as acute coronary syndromes, but also in the general population and in high-risk groups as patients with diabetes......, hypertension and coronary artery disease. This has of course raised interest for the use of the natriuretic peptides as a risk marker and for screening for heart failure with reduced systolic function in these populations. In symptomatic persons and in high risk populations, the natriuretic peptides have...... demonstrated a high sensitivity for ruling out the disease, if the right decision limits are choosen. Thus the number of normal echocardiographies can be reduced. More recently, the use in screening asymptomatic persons for left ventricular systolic dysfunction has gained more interest. In the unselected...

Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.

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Ito, Shingo; Ohtsuki, Sumio; Murata, Sho; Katsukura, Yuki; Suzuki, Hiroya; Funaki, Miho; Tachikawa, Masanori; Terasaki, Tetsuya

2014-01-01

Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.

Plant natriuretic peptides: Systemic regulators of plant homeostasis and defense that can affect cardiomyoblasts

KAUST Repository

Gehring, Christoph A.

2010-09-01

Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3′,5′-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apo-ptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs. Copyright © 2013 by The American Federation for Medical Research.

Plant natriuretic peptides: Systemic regulators of plant homeostasis and defense that can affect cardiomyoblasts

KAUST Repository

Gehring, Christoph A; Irving, Helen R.

2010-01-01

Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3′,5′-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apo-ptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs. Copyright © 2013 by The American Federation for Medical Research.

Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease

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Abhishek Sharma

2015-01-01

Full Text Available Biomarkers such as natriuretic peptides (NPs have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD.

Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease

Science.gov (United States)

Ahmed, Vaseem; Garg, Aakash; Aggarwal, Chirag

2015-01-01

Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD. PMID:26265794

The potential value of integrated natriuretic peptide and echo-guided heart failure management.

Science.gov (United States)

Scali, Maria Chiara; Simioniuc, Anca; Dini, Frank Lloyd; Marzilli, Mario

2014-07-18

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the

Amino-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein but not cystatin C predict cardiovascular events in male patients with peripheral artery disease independently of ambulatory pulse pressure.

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Skoglund, Per H; Arpegård, Johannes; Ostergren, Jan; Svensson, Per

2014-03-01

Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular (CV) events. We have previously shown that ambulatory pulse pressure (APP) predicts CV events in PAD patients. The biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cystatin C are related to a worse outcome in patients with CV disease, but their predictive values have not been studied in relation to APP. Blood samples and 24-hour measurements of ambulatory blood pressure were examined in 98 men referred for PAD evaluation during 1998-2001. Patients were followed for a median of 71 months. The outcome variable was CV events defined as either CV mortality or any hospitalization for myocardial infarction, stroke, or coronary revascularization. The predictive values of log(NT-proBNP), log(hs-CRP), and log(cystatin C) alone and together with APP were assessed by multivariable Cox regression. Area under the curve (AUC) and net reclassification improvement (NRI) were calculated compared with a model containing other significant risk factors. During follow-up, 36 patients had at least 1 CV event. APP, log(NT-proBNP), and log(hs-CRP) all predicted CV events in univariable analysis, whereas log(cystatin C) did not. In multivariable analysis log(NT-proBNP) (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 1.05-2.51) and log(hs-CRP) (HR = 1.63; 95% CI = 1.19-2.24) predicted events independently of 24-hour PP. The combination of log(NT-proBNP), log(hs-CRP), and average day PP improved risk discrimination (AUC = 0.833 vs. 0.736; P < 0.05) and NRI (37%; P < 0.01) when added to other significant risk factors. NT-proBNP and hs-CRP predict CV events independently of APP and the combination of hs-CRP, NT-proBNP, and day PP improves risk discrimination in PAD patients.

INTEGRATION OF BIOMARKERS INTO THE PRACTICE OF TREATING PATIENTS WITH HEART FAILURE: THE ROLE OF DETERMINING THE BLOOD LEVEL OF NATRIURETIC PEPTIDES

Directory of Open Access Journals (Sweden)

S. R. Gilyarevskiy

2017-01-01

Full Text Available A clinical role of biomarkers (especially, natriuretic peptides is discussed in the article. The most important evidences of clinical effectiveness of using biomarkers in patients with suspected heart failure and in patients with confirmed diagnose of heart failure are reviewed. The need to use natriuretic peptides in patients with takotsubo syndrome is discussed. Limited diagnostic value of using natriuretic peptides in renal dysfunction, as well as in other diseases in which the concentration of natriuretic peptides may increase in the absence of heart failure, is also discussed.

Hypercholesterolemia and apolipoprotein B expression: Regulation by selenium status

Directory of Open Access Journals (Sweden)

Bansal Mohinder P

2005-11-01

Full Text Available Abstract Background Apolipoprotein B (apoB contains ligand-binding domain for the binding of LDL to LDL-R site, which enables the removal of LDL from circulation. Our recent data showed that selenium (Se is involved in the lipid metabolism. The present study was aimed to understand the effect of Se deficiency (0.02 ppm and selenium supplementation (1 ppm on apoB expression in liver during hypercholesterolemia in male Sprague Dawley rats. Animals were fed with control and high cholesterol diet (2% for 1 and 2 months. ApoB levels by ELISA and protein expression by western blot was done. Hepatic LDL receptor (LDL-R activity (in vivo and mRNA expression by RT-PCR was monitored. Results In selenium deficiency and on high cholesterol diet (HCD feeding apoB levels increased and LDL-R expression decreased significantly after 2 months. On 1 ppm selenium supplementation apoB expression significantly decreased and LDL-R expression increased after 2 months. But after one month of treatment there was no significant change observed in apoB and LDL-R expression. Conclusion So the present study demonstrates that Se deficiency leads to up regulation of apoB expression during experimental hypercholesterolemia. Selenium supplementation upto 1 ppm leads to downregulation of apoB expression. Further, this study will highlight the nutritional value of Se supplementation in lipid metabolism.

B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

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Larimore Kevin

2012-06-01

Full Text Available Abstract Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.

Association of N-terminal pro-brain natriuretic peptide with cognitive function and depression in elderly people with type 2 diabetes.

Directory of Open Access Journals (Sweden)

Insa Feinkohl

Full Text Available Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF, cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS.Cross-sectional analysis of 1066 men and women aged 60-75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, 'g'. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower 'g' and higher depression scores (ß -0.09, 95% CI -0.13 to -0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p0.05 for 'g'; β 0.03, 95% CI -0.02 to 0.07, p>0.05 for depression scores.Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.

Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

Science.gov (United States)

Ding, Jiang-Hua; Chang, Yu-Sui

2012-08-01

Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Expression of C-type lectin receptor mRNA in chronic otitis media with cholesteatoma.

Science.gov (United States)

Kim, Sang Hoon; Han, Seung-Ho; Byun, Jae Yong; Park, Moon Suh; Kim, Young Il; Yeo, Seung Geun

2017-06-01

The levels of expression of various C-type lectin receptors (CLRs) messenger ribo nucleic acids (mRNAs) were significantly higher in cholesteatomas than in normal skin, suggesting that these CLRs may be involved in the pathogenesis of cholesteatoma. Altered expression of pattern recognition receptors may be associated with immune responses in patients with cholesteatoma. This study assessed the levels of expression of CLR mRNAs in normal skin and in cholesteatoma. Cholesteatoma specimens were obtained from 38 patients with acquired cholesteatoma. The levels of expression of various CLR mRNAs were assessed quantitatively using real-time RT-PCR (Reverse transcription polymerase chain reaction) and correlated with age, sex, the presence of bacteria, hearing level, frequency of surgery, and degree of ossicle destruction. The levels of CD206 (cluster of differentiation 206), DEC-205 (Dendritic and epithelial cell-205), MGL (monoacylglycerol lipase), CLEC5A (C-type lectin domain family 5 member A), Dectin-2 (dendrite cell-associated C-type lectin-2), BDCA2 (Blood dendritic cell antigen 2), Mincle, DCIR (dendritic cell immunoreceptor), Dectin-1, MICL (Myeloid inhibitory C type-like lectin), and CLEC12B (C-type lectin domain family 12, member B) mRNAs were significantly higher in cholesteatoma than in control skin samples (p C-type lectin domain family 5 member) and Dectin-1 mRNAs were significantly higher in cholesteatomas with ≥2 than ≤1 destroyed ossicles (p < 0.05), and the levels of MGL, Mincle, Dectin-1, and CLEC12B mRNAs were significantly higher in recurrent than initial cholesteatoma specimens (p < 0.05). The level of CLEC5A mRNAs was significantly higher in patients with severe than mild-to-moderate hearing loss (p < 0.05).

Role of Na+/K+-ATPase in Natriuretic Effect of Prolactin in a Model of Cholestasis of Pregnancy.

Science.gov (United States)

Abramicheva, P A; Balakina, T A; Bulaeva, O A; Guseva, A A; Lopina, O D; Smirnova, O V

2017-05-01

Participation of Na+/K+-ATPase in the natriuretic effect of prolactin in a cholestasis of pregnancy model was investigated. The Na+/K+-ATPase activity in rat kidney medulla, where active sodium reabsorption occurs, decreased in the model of cholestasis of pregnancy and other hyperprolactinemia types compared with intact animals. This effect was not connected with the protein level of α1- and β-subunits of Na+/K+-ATPase measured by Western blotting in the kidney medulla. Decrease in Na+/K+-ATPase activity in the kidney cortex was not significant, as well as decrease in the quantity of mRNA and proteins of the α1- and β-subunits of Na+/K+-ATPase. There were no correlations between the Na+/K+-ATPase activity and sodium clearance, although sodium clearance increased significantly in the model of cholestasis of pregnancy and other hyperprolactinemia groups under conditions of stable glomerular filtration rate measured by creatinine clearance. We conclude that the Na+/K+-ATPase is not the only mediator of the natriuretic effect of prolactin in the model of cholestasis of pregnancy.

Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.

Science.gov (United States)

Fox, Rebecca M; Vaishnavi, Aria; Maruyama, Rika; Andrew, Deborah J

2013-05-01

FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously.

Atrial natriuretic-like peptide and its prohormone within metasequoia.

Science.gov (United States)

Yang, Q; Gower, W R; Li, C; Chen, P; Vesely, D L

1999-07-01

Metasequoia glyptostroboides was one of the dominant conifers in North America, Asia, and Europe for more than 100 million years since the late Cretaceous Albian Age, but Quaternary glaciations drove the Metasequoia population to apparent extinction. A small pocket of Metasequoia, however, was found in central China in the 1940s representing the only surviving population of this "living fossil" species. Atrial natriuretic peptide, a 28-amino-acid peptide hormone that causes sodium and water excretion in animals, has been found to be part of the first peptide hormonal system in lower plants. The existence of this hormonal system has never been examined within trees of any genus. High-performance gel permeation chromatography of the leaves and stems (i.e., branches) of Metasequoia followed by atrial natriuretic peptide radioimmunoassay revealed an ANP-like peptide and its prohormone (i.e., approximately 13,000 mol wt) were present in both leaves and stems of this conifer. The elution profile of ANP-like peptide in stems of Metasequoia had a shoulder to the left of where pure synthetic ANP elutes suggesting the possibility of a slightly larger peptide eluting within this shoulder secondary to alternate processing of the ANP-like prohormone and similar to what occurs with the kidney of animals. The elution profile of ANP-like peptide in the leaves of Metasequoia revealed two peaks; one where ANP elutes and a second peak suggesting a smaller peptide that has been metabolically processed. The presence of the ANP-like prohormone strongly suggests that ANP-like gene expression is occurring in both leaves and stems of Metasequoia since this prohormone is the gene product of this hormonal system. The presence of the ANP-like hormonal system in trees implies that this hormonal system may have been present early in land plant evolution to allow trees to reach heights of greater than 30 feet where a water flow-enhancing substance is absolutely necessary for water flow to occur

Transcriptional activation of the tad type IVb pilus operon by PypB in Yersinia enterocolitica.

Science.gov (United States)

Schilling, Jennifer; Wagner, Karin; Seekircher, Stephanie; Greune, Lilo; Humberg, Verena; Schmidt, M Alexander; Heusipp, Gerhard

2010-07-01

Type IV pili are virulence factors in various bacteria and mediate, among other functions, the colonization of diverse surfaces. Various subclasses of type IV pili have been identified, but information on pilus expression, biogenesis, and the associated phenotypes is sparse for the genus Yersinia. We recently described the identification of PypB as a transcriptional regulator in Yersinia enterocolitica. Here we show that the pypB gene is associated with the tad locus, a genomic island that is widespread among bacterial and archaeal species. The genetic linkage of pypB with the tad locus is conserved throughout the yersiniae but is not found among other bacteria carrying the tad locus. We show that the genes of the tad locus form an operon in Y. enterocolitica that is controlled by PypB and that pypB is part of this operon. The tad genes encode functions necessary for the biogenesis of the Flp subfamily of type IVb pili initially described for Aggregatibacter actinomycetemcomitans to mediate a tight-adherence phenotype. In Y. enterocolitica, the Flp pilin protein shows some peculiarities in its amino acid sequence that imply similarities as well as differences compared to typical motifs found in the Flp subtype of type IVb pili. Flp is expressed and processed after PypB overproduction, resulting in microcolony formation but not in increased adherence to biotic or abiotic surfaces. Our data describe the transcriptional regulation of the tad type IVb pilus operon by PypB in Y. enterocolitica but fail to show most previously described phenotypes associated with this type of pilus in other bacteria.

Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

Science.gov (United States)

Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

2017-06-01

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

Urodilatin. A renal natriuretic peptide

International Nuclear Information System (INIS)

Carstens, Jan

1998-01-01

Development and validation of a radioimmunoassay for endogenous URO in urine and synthetic URO in plasma is described. The first obstacle to overcome was to produce an antibody specific for URO. A polyclonal URO antibody with a cross-reactivity with the structural highly homologous atrial natriuretic peptide (ANP) was developed by immunization of rabbits with the whole URO(95-126). Purification of the polyclonal URO antiserum with CNBr-activated Sepharose affinity chromatography was a simple way of producing a URO-specific antibody without cross-reactivity with ANP analogues. A reliable 125 I-labelled URO tracer was made with the Iodo-Gen method. Prior to the assay, the urine samples were prepared by ethanol with a recovery of unlabelled URO between 80 - 100% and the plasma samples were Sep-Pak C 18 extracted with a recovery of about 50%. The radioimmunoassay is performed in 3 days, using polyethylene glycol for separation. The sensitivity of the assay was improved by sample preparation and concentration, reducing the amount of tracer and late addition, reducing the amount of antibody and increasing the incubation time and lowering the temperature of incubation. The infusion rate of 20 ng URO kg -1 min -1 was most potential and well tolerated in healthy subjects. The short-term natriuretic and diuretic effects were closely associated with a significant diminished sodium reabsorption in the distal nephron. Further studies are needed to exploit the therapeutical potential of URO, for example in patients with sodium-water retaining disorders. The therapeutical dose range will probably be narrow due to the blood pressure lowering effect of URO with infusion rates higher than 20-30 ng kg -1 min -1 . (EHS)

Diagnostic Usefulness of N-terminal Pro-brain Natriuretic Peptide ...

African Journals Online (AJOL)

BACKGROUND: N-terminal pro-brain natriuretic peptide (NTproBNP) is useful in the diagnosis and management of adult patients with heart failure. OBJECTIVE: The objective of the study was to determine the usefulness of NT-proBNP in diagnosing congestive heart failure (CHF) in children and its correlation with left ...

Brain-natriuretic peptide and cyclic guanosine monophosphate as biomarkers of myxomatous mitral valve disease in dogs

DEFF Research Database (Denmark)

Moesgaard, Sophia Gry; Falk, Bo Torkel; Teerlink, Tom

2011-01-01

Elevations in the plasma concentrations of natriuretic peptides correlate with increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study correlates the severity of MMVD with the plasma concentrations of the biomarkers N-terminal fragment of the pro-brain-natriuretic peptide...... (NT-proBNP) and its second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the l-arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of nitric oxide availability. The study included 75 dogs sub-divided into five groups based on severity of MMVD as assessed...... by clinical examination and echocardiography. Plasma NT-proBNP and cGMP concentrations increased with increasing valve dysfunction and were significantly elevated in dogs with heart failure. The cGMP:NT-proBNP ratio decreased significantly in dogs with heart failure, suggesting the development of natriuretic...

The impact of right ventricular stroke work on B-type natriuretic peptide levels in patients with mitral stenosis undergoing percutaneous mitral valvuloplasty.

Science.gov (United States)

Esteves, William A M; Lodi-Junqueira, Lucas; Neto, Cirilo P Fonseca; Tan, Timothy C; Nascimento, Bruno R; Mehrotra, Praveen; Barbosa, Marcia M; Ribeiro, Antonio Luiz P; Nunes, Maria Carmo P

2013-10-01

We aimed to explore the relationship between brain natriuretic peptide (BNP) levels and right ventricular (RV) function in patients with mitral stenosis (MS), and to investigate the hemodynamic parameters that predict reduction of BNP levels after percutaneous mitral valvuloplasty (PMV). Few studies have evaluated BNP in the context of MS, specifically the impact of the RV stroke work (RVSW) on serum BNP levels has not been defined. Thirty patients with symptomatic rheumatic MS in sinus rhythm who were referred for a PMV were enrolled. Right and left heart pressures were obtained before and after valvuloplasty. RVSW index (RVSWI) was calculated by cardiac catheterization. Basal BNP levels were elevated in MS patients and correlated with several hemodynamic parameters including pulmonary pressure, pulmonary vascular resistance index, cardiac index (CI), and RVSWI. In multivariate analysis, CI and RVSWI were independent predictors of raised basal BNP levels. PMV resulted in a significant decrease in the RVSWI with a concurrent increase in CI (2.4 ± 0.43 to 2.9 ± 0.8 L/min/m(2), P = 0.010). Overall, plasma BNP levels significantly decreased from 124 (63/234) to 73 (48/148) pg/ml postvalvuloplasty. Multivariate analysis revealed that the reduction of left atrial (LA) pressure post-PMV was an independent predictor of change in BNP levels. Elevated baseline BNP level in MS patients was independently associated with CI and RVSWI. Plasma BNP levels were reduced after successful PMV, which was associated with the reduction of the LA pressure. © 2013, Wiley Periodicals, Inc.

Paradoxical expression of IL-28B mRNA in peripheral blood in human T-cell leukemia virus Type-1 mono-infection and co-infection with hepatitis C Virus

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Kamihira Shimeru

2012-02-01

Full Text Available Abstract Background Human T-cell leukemia virus type-1 (HTLV-1 carriers co-infected with and hepatitis C virus (HCV have been known to be at higher risk of their related diseases than mono-infected individuals. The recent studies clarified that IL-28B polymorphism rs8099917 is associated with not only the HCV therapeutic response by IFN, but also innate immunity and antiviral activity. The aim of our research was to clarify study whether IL-28B gene polymorphism (rs8099917 is associated with HTLV-1/HCV co-infection. Results The genotyping and viral-serological analysis for 340 individuals showed that IL-28B genotype distribution of rs8099917 SNP did not differ significantly by respective viral infection status. However, the IL-28B mRNA expression level was 3.8 fold higher in HTLV-1 mono-infection than HTLV-1/HCV co-infection. The high expression level was associated with TT (OR, 6.25, whiles the low expression was associated with co-infection of the two viruses (OR, 9.5. However, there was no association between down-regulation and ATL development (OR, 0.8. Conclusion HTLV-1 mono-infection up-regulates the expression of IL-28B transcripts in genotype-dependent manner, whiles HTLV-1/HCV co-infection down-regulates regardless of ATL development.

Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization.

Science.gov (United States)

Nagai-Okatani, Chiaki; Kangawa, Kenji; Minamino, Naoto

2017-07-01

Atrial natriuretic peptide (ANP) is primarily produced in the heart tissue and plays a pivotal role in maintaining cardiovascular homeostasis in endocrine and autocrine/paracrine systems and has clinical applications as a biomarker and a therapeutic agent for cardiac diseases. ANP is synthesized by atrial cardiomyocytes as a preprohormone that is processed by a signal peptidase and stored in secretory granules as a prohormone. Subsequent proteolytic processing of ANP by corin during the secretion process results in a bioactive form consisting of 28 amino acid residues. Mechanical stretch of the atrial wall and multiple humoral factors directly stimulates the transcription and secretion of ANP. Secreted ANP elicits natriuretic and diuretic effects via cyclic guanosine monophosphate produced through binding to the guanylyl cyclase-A/natriuretic peptide receptor-A. Circulating ANP is subjected to rapid clearance by a natriuretic peptide receptor-C-mediated mechanism and proteolytic degradation by neutral endopeptidase. In humans, ANP is present as three endogenous molecular forms: bioactive α-ANP, a homodimer of α-ANP designated as β-ANP, and an ANP precursor designated as proANP (also referred to as γ-ANP). The proANP and especially β-ANP, as minor forms in circulation, are notably increased in patients with cardiac diseases, suggesting the utility of monitoring the pathophysiological conditions that result in abnormal proANP processing that cannot be monitored by inactive N-terminal proANP-related fragments. Emerging plate-based sandwich immunoassays for individual quantitation of the three ANP forms enables evaluation of diagnostic implications and net ANP bioactivity. This new tool may provide further understanding in the pathophysiology of cardiac diseases. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

SCF(KMD) controls cytokinin signaling by regulating the degradation of type-B response regulators.

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Kim, Hyo Jung; Chiang, Yi-Hsuan; Kieber, Joseph J; Schaller, G Eric

2013-06-11

Cytokinins are plant hormones that play critical roles in growth and development. In Arabidopsis, the transcriptional response to cytokinin is regulated by action of type-B Arabidopsis response regulators (ARRs). Although central elements in the cytokinin signal transduction pathway have been identified, mechanisms controlling output remain to be elucidated. Here we demonstrate that a family of F-box proteins, called the kiss me deadly (KMD) family, targets type-B ARR proteins for degradation. KMD proteins form an S-phase kinase-associated PROTEIN1 (SKP1)/Cullin/F-box protein (SCF) E3 ubiquitin ligase complex and directly interact with type-B ARR proteins. Loss-of-function KMD mutants stabilize type-B ARRs and exhibit an enhanced cytokinin response. In contrast, plants with elevated KMD expression destabilize type-B ARR proteins leading to cytokinin insensitivity. Our results support a model in which an SCF(KMD) complex negatively regulates cytokinin responses by controlling levels of a key family of transcription factors.

Plasma C-type natriuretic peptide as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome.

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Jing Lin

Full Text Available POTS is a global public-health disease, but predictor for therapeutic response to metoprolol in children with POTS is lacking. This study was designed to investigate predictive value of plasma C-type natriuretic peptide (CNP in the therapeutic efficacy of metoprolol on postural tachycardia syndrome (POTS in children. Totally 34 children with POTS and 27 healthy children were included in the study. The head-up test or head-up tilt test was used to check heart rate and blood pressure from supine to upright in subjects. A double antibody (competitive sandwich immunoluminometric assay was used to detect plasma CNP. Metoprolol was used to treat children with POTS. The difference in plasma concentrations of CNP between responders and non-responders was compared. An ROC curve was used to analyze plasma CNP to predict efficacy of metoprolol on POTS in children. Plasma CNP in children with POTS was significantly higher than that of healthy children [(51.9 ± 31.4 vs. (25.1 ± 19.1 pg/ml, P 32.55 pg/ml yielded a sensitivity of 95.8% and specificity of 70% in predicting therapeutic efficacy of metoprolol on POTS children. Plasma CNP might serve as a useful predictor for the therapeutic efficacy of metoprolol on POTS in children.

Cell type-specific translational repression of Cyclin B during meiosis in males.

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Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T

2015-10-01

The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I. © 2015. Published by The Company of Biologists Ltd.

Plasma Atrial Natriuretic Peptide as a non-invasive biochemical ...

African Journals Online (AJOL)

Plasma Atrial Natriuretic Peptide as a non-invasive biochemical marker of dyspnoea in congestive heart failure patients. ... University of Mauritius Research Journal ... score assessed by a 10 graded visual analogue scale in the control group (mean score = 1) and an increased from 1.6 to 6.4 in the heart failure patients.

Effects of Oral Contraceptives on Natriuretic Peptide Levels in Women with Hypothalamic Amenorrhea: A Pilot Study

OpenAIRE

Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K.

2011-01-01

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60 – 75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives increases natriuretic peptide levels and that end-of-study free testosterone levels are inversely associated with NT-proBNP levels, consistent with the hypothesis that ...

Flow cytometric analysis of immunoglobulin heavy chain expression in B-cell lymphoma and reactive lymphoid hyperplasia

Science.gov (United States)

Grier, David D; Al-Quran, Samer Z; Cardona, Diana M; Li, Ying; Braylan, Raul C

2012-01-01

The diagnosis of B-cell lymphoma (BCL) is often dependent on the detection of clonal immunoglobulin (Ig) light chain expression. In some BCLs, the determination of clonality based on Ig light chain restriction may be difficult. The aim of our study was to assess the utility of flow cytometric analysis of surface Ig heavy chain (HC) expression in lymphoid tissues in distinguishing lymphoid hyperplasias from BCLs, and also differentiating various BCL subtypes. HC expression on B-cells varied among different types of hyperplasias. In follicular hyperplasia, IgM and IgD expression was high in mantle cells while germinal center cells showed poor HC expression. In other hyperplasias, B cell compartments were blurred but generally showed high IgD and IgM expression. Compared to hyperplasias, BCLs varied in IgM expression. Small lymphocytic lymphomas had lower IgM expression than mantle cell lymphomas. Of importance, IgD expression was significantly lower in BCLs than in hyperplasias, a finding that can be useful in differentiating lymphoma from reactive processes. PMID:22400070

Factors Associated With Natriuretic Peptide Testing in Patients Presenting to Emergency Departments With Suspected Heart Failure.

Science.gov (United States)

Sepehrvand, Nariman; Bakal, Jeffrey A; Lin, Meng; McAlister, Finlay; Wesenberg, James C; Ezekowitz, Justin A

2016-08-01

Testing for natriuretic peptides (NPs) such as brain natriuretic peptide (BNP) or N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the emergency department (ED) assists in the evaluation of patients with acute heart failure (HF). The aim of this study was to investigate factors related to the use of NP testing in the ED in a large population-based sample in Canada. This was a retrospective cohort study using linked administrative data from Alberta in 2012. Patients were included if they had testing for an NP in the ED; a comparator group with HF but without NP testing was also included. Of the 16,223 patients in the cohort, 5793 were patients with HF (n = 3148 tested and n = 2645 not tested for NPs) and 10,430 were patients without HF but who were tested for NPs. Patients without HF who were tested for NPs had respiratory disease (34%), non-HF cardiovascular diseases (13%), and other conditions (52%). Patients with HF who were tested had a higher rate of hospital admission from the ED (78.4% vs 62.2%; P < 0.001) and lower 7-day and 90-day repeated ED visit rates compared with those who were not tested. Among patients with HF, male sex, being an urban resident, being seen by an emergency medicine or cardiology specialist, and being seen in hospitals with medium ED visit volumes were associated with increased likelihood of testing for NPs. Several factors, including the type of provider and ED clinical volume, influenced the use of NP testing in routine ED practice. Standardization of an NP testing strategy in clinical practice would be useful for health care systems. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The biofilm-specific antibiotic resistance gene ndvB is important for expression of ethanol oxidation genes in Pseudomonas aeruginosa biofilms.

Science.gov (United States)

Beaudoin, Trevor; Zhang, Li; Hinz, Aaron J; Parr, Christopher J; Mah, Thien-Fah

2012-06-01

Bacteria growing in biofilms are responsible for a large number of persistent infections and are often more resistant to antibiotics than are free-floating bacteria. In a previous study, we identified a Pseudomonas aeruginosa gene, ndvB, which is important for the formation of periplasmic glucans. We established that these glucans function in biofilm-specific antibiotic resistance by sequestering antibiotic molecules away from their cellular targets. In this study, we investigate another function of ndvB in biofilm-specific antibiotic resistance. DNA microarray analysis identified 24 genes that were responsive to the presence of ndvB. A subset of 20 genes, including 8 ethanol oxidation genes (ercS', erbR, exaA, exaB, eraR, pqqB, pqqC, and pqqE), was highly expressed in wild-type biofilm cells but not in ΔndvB biofilms, while 4 genes displayed the reciprocal expression pattern. Using quantitative real-time PCR, we confirmed the ndvB-dependent expression of the ethanol oxidation genes and additionally demonstrated that these genes were more highly expressed in biofilms than in planktonic cultures. Expression of erbR in ΔndvB biofilms was restored after the treatment of the biofilm with periplasmic extracts derived from wild-type biofilm cells. Inactivation of ethanol oxidation genes increased the sensitivity of biofilms to tobramycin. Together, these results reveal that ndvB affects the expression of multiple genes in biofilms and that ethanol oxidation genes are linked to biofilm-specific antibiotic resistance.

Major histocompatibility complex class I-related chain A/B (MICA/B) expression in tumor tissue and serum of pancreatic cancer: Role of uric acid accumulation in gemcitabine-induced MICA/B expression

International Nuclear Information System (INIS)

Xu, Xiulong; Rao, Geetha S; Groh, Veronika; Spies, Thomas; Gattuso, Paolo; Kaufman, Howard L; Plate, Janet; Prinz, Richard A

2011-01-01

Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind the immunoreceptor NKG2D and play an important role in mediating the cyotoxicity of NK and T cells. In this study, we sought to study MICA/B expression in pancreatic cancer and to determine whether and how genotoxic drugs such as gemcitabine can affect MICA/B expression and natural killer cytotoxity. Seven pancreatic cancer cell lines were analyzed for MICA/B expression by flow cytometry and for their sensitivity to NK-92 cell killing by a 51 Cr release assay. MICA/B expression in tumor tissues and sera of pancreatic cancer was analyzed by immunohistochemical staining (IHC) and ELISA, respectively. Two MICA/B-positive cell lines were sensitive to the cytotoxic activity of NK-92 cells. Other two MICA/B-positive cell lines and three MICA/B-negative cell lines were resistant to NK-92 cell killing. MICA/B expression was positive in 17 of 25 (68%) pancreatic ductal adenocarcinomas but not in normal pancreatic ductal epithelial cells. Serum MICA/B levels were significantly elevated in patients with pancreatic adenocarcinomas but did not correlate with the stage of pancreatic cancer and patient survival. Gemcitabine therapy led to increased serum MICA levels in 6 of 10 patients with detectable serum MICA. Allopurinol, an inhibitor of xanthine oxidoreductase that converts xanthine to uric acid, blocked uric acid production, MICA/B expression, and sensitivity to NK-92 cell killing toward a PANC-1 cancer cell line exposed to radiation and two genotoxic drugs, gemcitabine and 5-fluorouracil. The levels of MICA/B expression in serum and tissue of pancreatic cancer are elevated. DNA damage-induced MICA/B expression is mediated through increased uric acid production

Major histocompatibility complex class I-related chain A/B (MICA/B expression in tumor tissue and serum of pancreatic cancer: Role of uric acid accumulation in gemcitabine-induced MICA/B expression

Directory of Open Access Journals (Sweden)

Kaufman Howard L

2011-05-01

Full Text Available Abstract Background Major histocompatibility complex class I-related chain A and B (MICA/B are two stress-inducible ligands that bind the immunoreceptor NKG2D and play an important role in mediating the cyotoxicity of NK and T cells. In this study, we sought to study MICA/B expression in pancreatic cancer and to determine whether and how genotoxic drugs such as gemcitabine can affect MICA/B expression and natural killer cytotoxity. Methods Seven pancreatic cancer cell lines were analyzed for MICA/B expression by flow cytometry and for their sensitivity to NK-92 cell killing by a 51Cr release assay. MICA/B expression in tumor tissues and sera of pancreatic cancer was analyzed by immunohistochemical staining (IHC and ELISA, respectively. Results Two MICA/B-positive cell lines were sensitive to the cytotoxic activity of NK-92 cells. Other two MICA/B-positive cell lines and three MICA/B-negative cell lines were resistant to NK-92 cell killing. MICA/B expression was positive in 17 of 25 (68% pancreatic ductal adenocarcinomas but not in normal pancreatic ductal epithelial cells. Serum MICA/B levels were significantly elevated in patients with pancreatic adenocarcinomas but did not correlate with the stage of pancreatic cancer and patient survival. Gemcitabine therapy led to increased serum MICA levels in 6 of 10 patients with detectable serum MICA. Allopurinol, an inhibitor of xanthine oxidoreductase that converts xanthine to uric acid, blocked uric acid production, MICA/B expression, and sensitivity to NK-92 cell killing toward a PANC-1 cancer cell line exposed to radiation and two genotoxic drugs, gemcitabine and 5-fluorouracil. Conclusions The levels of MICA/B expression in serum and tissue of pancreatic cancer are elevated. DNA damage-induced MICA/B expression is mediated through increased uric acid production.

Cocoa flavanols reduce N‐terminal pro‐B‐type natriuretic peptide in patients with chronic heart failure

Science.gov (United States)

De Palma, Rodney; Sotto, Imelda; Wood, Elizabeth G.; Khan, Noorafza Q.; Butler, Jane; Johnston, Atholl; Rothman, Martin T.

2015-01-01

Abstract Aims Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) as an index of improved cardiac function. Methods and results Thirty‐two patients with chronic HF, stable on guideline‐directed medical therapy, were randomized to consume 50 g/day of high‐flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low‐flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty‐four patients completed the study. After 4 weeks of HFDC, NT‐proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (−44 ± 69%), LFDC (−33 ± 72%), and follow‐up (−41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (−6.7 ± 10.1 mmHg). Conclusions Reductions in blood pressure and NT‐proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF. PMID:27588209

Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

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Idalia Garza-Veloz

2015-01-01

Full Text Available Background. Acute lymphoblastic leukemia type B (B-ALL is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL. Methods. 219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction. Results. Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (P values < 0.05. There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (P values < 0.05 and odds ratio ranges: 3.73–27. The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (P values < 0.05. Conclusions. Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

Science.gov (United States)

Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

2016-01-01

The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

Synthesis of Heparan Sulfate with Cyclophilin B-binding Properties Is Determined by Cell Type-specific Expression of Sulfotransferases*

Science.gov (United States)

Deligny, Audrey; Denys, Agnès; Marcant, Adeline; Melchior, Aurélie; Mazurier, Joël; van Kuppevelt, Toin H.; Allain, Fabrice

2010-01-01

Cyclophilin B (CyPB) induces migration and adhesion of T lymphocytes via a mechanism that requires interaction with 3-O-sulfated heparan sulfate (HS). HS biosynthesis is a complex process with many sulfotransferases involved. N-Deacetylases/N-sulfotransferases are responsible for N-sulfation, which is essential for subsequent modification steps, whereas 3-O-sulfotransferases (3-OSTs) catalyze the least abundant modification. These enzymes are represented by several isoforms, which differ in term of distribution pattern, suggesting their involvement in making tissue-specific HS. To elucidate how the specificity of CyPB binding is determined, we explored the relationships between the expression of these sulfotransferases and the generation of HS motifs with CyPB-binding properties. We demonstrated that high N-sulfate density and the presence of 2-O- and 3-O-sulfates determine binding of CyPB, as evidenced by competitive experiments with heparin derivatives, soluble HS, and anti-HS antibodies. We then showed that target cells, i.e. CD4+ lymphocyte subsets, monocytes/macrophages, and related cell lines, specifically expressed high levels of NDST2 and 3-OST3 isoforms. Silencing the expression of NDST1, NDST2, 2-OST, and 3-OST3 by RNA interference efficiently decreased binding and activity of CyPB, thus confirming their involvement in the biosynthesis of binding sequences for CyPB. Moreover, we demonstrated that NDST1 was able to partially sulfate exogenous substrate in the absence of NDST2 but not vice versa, suggesting that both isoenzymes do not have redundant activities but do have rather complementary activities in making N-sulfated sequences with CyPB-binding properties. Altogether, these results suggest a regulatory mechanism in which cell type-specific expression of certain HS sulfotransferases determines the specific binding of CyPB to target cells. PMID:19940140

Synthesis of heparan sulfate with cyclophilin B-binding properties is determined by cell type-specific expression of sulfotransferases.

Science.gov (United States)

Deligny, Audrey; Denys, Agnès; Marcant, Adeline; Melchior, Aurélie; Mazurier, Joël; van Kuppevelt, Toin H; Allain, Fabrice

2010-01-15

Cyclophilin B (CyPB) induces migration and adhesion of T lymphocytes via a mechanism that requires interaction with 3-O-sulfated heparan sulfate (HS). HS biosynthesis is a complex process with many sulfotransferases involved. N-Deacetylases/N-sulfotransferases are responsible for N-sulfation, which is essential for subsequent modification steps, whereas 3-O-sulfotransferases (3-OSTs) catalyze the least abundant modification. These enzymes are represented by several isoforms, which differ in term of distribution pattern, suggesting their involvement in making tissue-specific HS. To elucidate how the specificity of CyPB binding is determined, we explored the relationships between the expression of these sulfotransferases and the generation of HS motifs with CyPB-binding properties. We demonstrated that high N-sulfate density and the presence of 2-O- and 3-O-sulfates determine binding of CyPB, as evidenced by competitive experiments with heparin derivatives, soluble HS, and anti-HS antibodies. We then showed that target cells, i.e. CD4+ lymphocyte subsets, monocytes/macrophages, and related cell lines, specifically expressed high levels of NDST2 and 3-OST3 isoforms. Silencing the expression of NDST1, NDST2, 2-OST, and 3-OST3 by RNA interference efficiently decreased binding and activity of CyPB, thus confirming their involvement in the biosynthesis of binding sequences for CyPB. Moreover, we demonstrated that NDST1 was able to partially sulfate exogenous substrate in the absence of NDST2 but not vice versa, suggesting that both isoenzymes do not have redundant activities but do have rather complementary activities in making N-sulfated sequences with CyPB-binding properties. Altogether, these results suggest a regulatory mechanism in which cell type-specific expression of certain HS sulfotransferases determines the specific binding of CyPB to target cells.

bHLH-O proteins balance the self-renewal and differentiation of Drosophila neural stem cells by regulating Earmuff expression.

Science.gov (United States)

Li, Xiaosu; Chen, Rui; Zhu, Sijun

2017-11-15

Balancing self-renewal and differentiation of stem cells requires differential expression of self-renewing factors in two daughter cells generated from the asymmetric division of the stem cells. In Drosophila type II neural stem cell (or neuroblast, NB) lineages, the expression of the basic helix-loop-helix-Orange (bHLH-O) family proteins, including Deadpan (Dpn) and E(spl) proteins, is required for maintaining the self-renewal and identity of type II NBs, whereas the absence of these self-renewing factors is essential for the differentiation of intermediate neural progenitors (INPs) generated from type II NBs. Here, we demonstrate that Dpn maintains type II NBs by suppressing the expression of Earmuff (Erm). We provide evidence that Dpn and E(spl) proteins suppress Erm by directly binding to C-sites and N-boxes in the cis-regulatory region of erm. Conversely, the absence of bHLH-O proteins in INPs allows activation of erm and Erm-mediated maturation of INPs. Our results further suggest that Pointed P1 (PntP1) mediates the dedifferentiation of INPs resulting from the loss of Erm or overexpression of Dpn or E(spl) proteins. Taken together, these findings reveal mechanisms underlying the regulation of the maintenance of type II NBs and differentiation of INPs through the differential expression of bHLH-O family proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure.

Science.gov (United States)

Fu, Shihui; Ping, Ping; Wang, Fengqi; Luo, Leiming

2018-01-01

As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body's own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained

Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.

LENUS (Irish Health Repository)

Watson, Chris J

2011-03-01

Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

Cardiomyocyte expression and cell-specific processing of procholecystokinin

DEFF Research Database (Denmark)

Gøtze, Jens P.; Johnsen, Anders H.; Kistorp, Caroline

2015-01-01

has only been suggested using transcriptional measures or methods, with the post-translational phase of gene expression unaddressed. In this study, we examined the cardiac expression of the CCK gene in adult mammals and its expression at the protein level. Using quantitative PCR, a library of sequence......-specific pro-CCK assays, peptide purification, and mass spectrometry, we demonstrate that the mammalian heart expresses pro-CCK in amounts comparable to natriuretic prohormones and processes it to a unique, triple-sulfated, and N-terminally truncated product distinct from intestinal and cerebral CCK peptides...

Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

Energy Technology Data Exchange (ETDEWEB)

Cheng, Li-Chuan; Li, Lih-Ann, E-mail: lihann@nhri.org.tw

2012-02-01

CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

International Nuclear Information System (INIS)

Cheng, Li-Chuan; Li, Lih-Ann

2012-01-01

CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

Science.gov (United States)

Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

2012-01-01

African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

Type B drum packages

International Nuclear Information System (INIS)

McCoy, J.C.

1994-08-01

The Type B drum packages (TBD) are conceptualized as a family of containers in which a single 208 L or 114 L (55 gal or 30 gal) drum containing Type B quantities of radioactive material (RAM) can be packaged for shipment. The TBD containers are being developed to fill a void in the packaging and transportation capabilities of the U.S. Department of Energy as no container packaging single drums of Type B RAM exists offering double containment. Several multiple-drum containers currently exist, as well as a number of shielded casks, but the size and weight of these containers present many operational challenges for single-drum shipments. As an alternative, the TBD containers will offer up to three shielded versions (light, medium, and heavy) and one unshielded version, each offering single or optional double containment for a single drum. To reduce operational complexity, all versions will share similar design and operational features where possible. The primary users of the TBD containers are envisioned to be any organization desiring to ship single drums of Type B RAM, such as laboratories, waste retrieval activities, emergency response teams, etc. Currently, the TBD conceptual design is being developed with the final design and analysis to be completed in 1995 to 1996. Testing and certification of the unshielded version are planned to be completed in 1996 to 1997 with production to begin in 1997 to 1998

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload : correlation between plasma neurohormones and right ventricular dysfunction

NARCIS (Netherlands)

Tulevski, I.I.; Groenink, M; van der Wall, EE; van Veldhuisen, DJ; Boomsma, F; Hirsch, A; Lemkes, JS; Mulder, BJM; Stoker, J

Objective-To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction. Setting-Tertiary cardiovascular referral centre. Methods-Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction

NARCIS (Netherlands)

Tulevski, I. I.; Groenink, M.; van der Wall, E. E.; van Veldhuisen, D. J.; Boomsma, F.; Stoker, J.; Hirsch, A.; Lemkes, J. S.; Mulder, B. J.

2001-01-01

OBJECTIVE: To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction. SETTING: Tertiary cardiovascular referral centre. METHODS: Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were

Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

International Nuclear Information System (INIS)

Kaznelson, Dorte Wissing; Bruun, Silas; Monrad, Astrid; Gjerloev, Simon; Birk, Jesper; Roepke, Carsten; Norrild, Bodil

2004-01-01

Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induction of cell death. We have used the osteosarcoma cell line U2OS cells provided with E7 and the cdk2 inhibitor p21 (cip1/waf1) under inducible control, as a model system for the analysis of E7-mediated apoptosis. Our data shows that simultaneous expression of E7 and p21 proteins induces cell death, possibly because of conflicting growth control. Interestingly, E7/p21-induced cell death is associated with the activation of a newly identified mediator of apoptosis, namely cathepsin B. Activation of the cellular caspases is undetectable in cells undergoing E7/p21-induced apoptosis. To our knowledge, this is the first time a role for cathepsin B is reported in HPV-induced apoptotic signalling

Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB.

Science.gov (United States)

Ricciardolo, F L M; Petecchia, L; Sorbello, V; Di Stefano, A; Usai, C; Massaglia, G M; Gnemmi, I; Mognetti, B; Hiemstra, P S; Sterk, P J; Sabatini, F

2016-03-01

Bradykinin (BK) mediates acute allergic asthma and airway remodelling. Nuclear factor-kappa B (NF-kB) is potentially involved in BK B2 receptor (B2R) regulation. In this observational cross-sectional study, B2R and NF-kB expression was evaluated in bronchial biopsies from mild asthmatics (after diluent/allergen challenge) and healthy controls, examining the role of NF-kB in B2R expression in primary human fibroblasts from normal and asthmatic subjects (HNBFb and HABFb). B2R and NF-kB (total and nuclear) expression was analysed by immunohistochemistry in biopsies from 10 mild intermittent asthmatics (48 h after diluent/allergen challenge) and 10 controls undergoing bronchoscopy. B2R co-localization in 5B5(+) and αSMA(+) mesenchymal cells was studied by immunofluorescence/confocal microscopy, and B2R expression in HABFb/HNBFb incubated with interleukin (IL)-4/IL-13 with/without BK, and after NF-kB inhibitor, by Western blotting. Bronchial mucosa B2R and nuclear NF-kB expression was higher in asthmatics after diluent (B2R only) and allergen challenge than in controls (P kB (total and nuclear) increased after allergen compared with after diluent (P kB inhibitor (P kB expression. NF-kB inhibitor blocked IL-4/IL-13-induced increase in B2R expression in cultured fibroblasts, suggesting a role as potential anti-asthma drug. © 2015 John Wiley & Sons Ltd.

Comparative study of the effects of PM1-induced oxidative stress on autophagy and surfactant protein B and C expressions in lung alveolar type II epithelial MLE-12 cells.

Science.gov (United States)

Bai, Ru; Guan, Longfei; Zhang, Wei; Xu, Jinxia; Rui, Wei; Zhang, Fang; Ding, Wenjun

2016-12-01

There is a strong link between smaller air pollution particles and a range of serious health conditions. Thus, there is a need for understanding the impacts of airborne fine particulate matter (PM) with an aerodynamic diameter of PM1) on lung alveolar epithelial cells. In the present study, mouse lung epithelial type II cell MLE-12 cells were used to examine the intracellular oxidative responses and the surfactant protein expressions after exposure to various concentrations of PM1 collected from an urban site and a steel-factory site (referred as uPM1 and sPM1 hereafter, respectively). Physicochemical characterization of PM1 was performed by using scanning electron microscopy and transmission electron microscopy. Cytotoxicity and autophagy induced by PM1 were assessed by using comprehensive approaches after MLE-12 cells were exposed to different concentrations of PM1 for various times. Expression of surfactant proteins B and C in MLE-12 cells was determined by Western blotting. All of the tested PM1 induced cytotoxicity evidenced by significant decrease of cell viability and increase of lactate dehydrogenase (LDH) release in a time- and concentration-dependent manner in the exposed cells compared with the unexposed cells. A similar pattern of increase of intercellular reactive oxygen species (ROS) generation and decrease of superoxide dismutase (SOD) and catalase (CAT) activities was also observed. PM1-induced autophagy was evidenced by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3II, and increased levels of beclin1. Data from Western blotting showed significant decrease of surfactant protein B and C expressions. Relatively high concentrations of transition metals, including Fe, Cu and Mn, may be responsible for the higher toxicity of sPM1 compared with uPM1. Moreover, pretreatment with N-acetylcysteine (NAC) or Chelex (a metal chelating agent, which removes a large suite of metals from PM1) prevented the increase of

The M142T mutation causes B3 phenotype: three cases and an in vitro expression study.

Science.gov (United States)

Cho, Duck; Shin, Dong-Jun; Yazer, Mark Harris; Ihm, Chun-Hwa; Hur, Young-Moon; Kee, Seung-Jung; Kim, Soo-Hyun; Shin, Myung-Geun; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook

2010-02-01

The B3 phenotype is the most common B subtype in Korea. The B305 allele (425 T>C, M142T) was first reported in 2 Chinese individuals; however, it has not yet been reported in the Koreans, and the impact of the M142T mutation on the expression of the B3 phenotype has also not been studied. To resolve an ABO discrepancy between a group O neonate and her group O father and A(1)B(3) mother, blood samples from these individuals and other family members were referred to our laboratory for ABO gene analysis. The B305 allele was discovered in the neonate (B305/O01), her mother (A102/ B305), and her maternal aunt (B305/O02), while her father was typed as O01/O02. Transient transfection experiments were performed in HeLa cells using the B305 allele synthesized by site-directed mutagenesis; flow cytometric analysis revealed that this transfect expressed 35.5% of the total B antigen produced by the B101 allele transfect. For comparison, Bx01 allele transfects were also created, and they expressed 11.4% of the total B antigen expressed on the surface of B101 transfects. These experiments demonstrate that the M142T (425 T>C) mutation is responsible for the B subtype phenotype produced by the B305 allele.

Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death.

Science.gov (United States)

Li, Zheng; Wang, Ji-Wei; Wang, Wei-Zhi; Zhi, Xiao-Fei; Zhang, Qun; Li, Bo-Wen; Wang, Lin-Jun; Xie, Kun-Ling; Tao, Jin-Qiu; Tang, Jie; Wei, Song; Zhu, Yi; Xu, Hao; Zhang, Dian-Cai; Yang, Li; Xu, Ze-Kuan

2016-10-01

Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

Science.gov (United States)

Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

2015-12-01

Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Salinity-dependent in vitro effects of homologous natriuretic peptides on the pituitary-interrenal axis in eels.

Science.gov (United States)

Ventura, Albert; Kusakabe, Makoto; Takei, Yoshio

2011-08-01

We examined the effects of atrial, B-type, ventricular and C-type natriuretic peptides (ANP, BNP, VNP and CNP1, 3, 4) on cortisol secretion from interrenal tissue in vitro in both freshwater (FW) and seawater (SW)-acclimated eels. We first localized the interrenal and chromaffin cells in the eel head kidney using cell specific markers (cholesterol side-chain cleavage enzyme (P450ssc) and tyrosine hydroxylase (TH), respectively) and established the in vitro incubation system for eel interrenal tissue. Unexpectedly, none of the NPs given alone to the interrenal tissue of FW and SW eels stimulated cortisol secretion. However, ANP and VNP, but not BNP and three CNPs, enhanced the steroidogenic action of ACTH in SW interrenal preparations, while CNP1 and CNP4, but not ANP, BNP, VNP and CNP3, potentiated the ACTH action in FW preparations. These salinity dependent effects of NPs are consistent with the previous in vivo study in the eel where endogenous ACTH can act with the injected NPs. 8-Br-cGMP also enhanced the ACTH action in both FW and SW eel preparations, suggesting that the NP actions were mediated by the guanylyl cyclase-coupled NP receptors (GC-A and B) that were localized in the eel interrenal. Further, ANP and CNP1 stimulated ACTH secretion from isolated pituitary glands of SW and/or FW eels. In summary, the present study revealed complex mechanisms of NP action on corticosteroidogenesis through the pituitary-interrenal axis in eels, thereby providing a deeper insight into the role of the NP family in the acclimation of this euryhaline teleost to diverse salinity environments. Copyright © 2011 Elsevier Inc. All rights reserved.

Identification of YB-1 as a regulator of PTP1B expression: implications for regulation of insulin and cytokine signaling

Science.gov (United States)

Fukada, Toshiyuki; Tonks, Nicholas K.

2003-01-01

Changes in expression of PTP1B, the prototypic protein tyrosine phosphatase, have been associated with various human diseases; however, the mechanisms by which PTP1B expression is regulated have not been defined. We have identified an enhancer sequence within the PTP1B promoter which serves as a binding site for the transcription factor Y box-binding protein-1 (YB-1). Overexpression of YB-1 resulted in increased levels of PTP1B. Furthermore, depletion of YB-1 protein, by expression of a specific antisense construct, led to an ∼70% decrease in expression of PTP1B, but no change in the level of its closest relative, TC-PTP. Expression of antisense YB-1 resulted in increased sensitivity to insulin and enhanced signaling through the cytokine receptor gp130, which was suppressed by re-expression of PTP1B. Finally, we observed a correlation between the expression of PTP1B and that of YB-1 in cancer cell lines and an animal model of type II diabetes. Our data reveal an important role for YB-1 as a regulator of PTP1B expression, and further highlight PTP1B as a critical regulator of insulin- and cytokine-mediated signal transduction. PMID:12554649

Expression and significance of TRAIL and NF-kB in osteosarcoma

International Nuclear Information System (INIS)

Du Xiumin; You Murong; Qi Falian; Hu Chengjin

2005-01-01

To investigate the relationship between expressions of TRAIL, NF-kB and cell proliferation in human osteosarcomas, the expressions of TRAIL and NF-kB in 16 cases of osteosarcoma, 5 cases of giant cell tumor of bone and 6 cases of chondrosarcoma were studied by flow cytometry. The expressions of TRAIL and NF-kB in osteosarcomas of different differentiation states were higher than those in other two kinds of tumors significantly in our study(P 0.05). The expressions of TRAIL and NF-kB in chondrosarcoma and giant cell tumor of bone were not different significantly(P>0.05). The higher expression of TRAIL in osteosarcoma with different differentiation states could not induce apoptosis because of the higher expression of NF-kB. NF-kB may restrain the apoptosis of tumor cells by regulating the NF-kB- induced apoptosis path way in osteosarcoma. (authors)

Packaging design criteria for the Type B Drum

International Nuclear Information System (INIS)

Edwards, W.S.; Smith, R.J.; Wells, A.H.

1995-09-01

The Type B Drum package is a transportation cask capable of shipping a single 55-gal (208 L) drum of transuranic (TRU) waste. The Type B Drum is smaller than existing certified packages, such as the TRUPACT-II cask, but will allow payloads with higher thermal and gas generation rates, thus providing greater operational flexibility. The Type B Drum package has double containment so that plutonium contents and other radioactive material may be transported in Type B quantities. Conceptual designs of unshielded and shielded versions of the Type B Drum were completed in Report on the Conceptual Design of the Unshielded Type B Drum Packaging and Report on the Conceptual Design of the Shielded type B Drum Packaging (WEC 1994a, WEC 1994b), which demonstrated the Type B Drum to be a viable packaging system. A Type B package containment system must withstand the normal conditions of transport and the hypothetical accident conditions, which include a 9-m (30-ft) drop onto an unyielding surface and a 1-m (3-ft) drop onto a 15-cm (6-in.) diameter pin, and a fire and immersion scenarios

A systematic expression analysis implicates Plexin-B2 and its ligand Sema4C in the regulation of the vascular and endocrine system.

Science.gov (United States)

Zielonka, Matthias; Xia, Jingjing; Friedel, Roland H; Offermanns, Stefan; Worzfeld, Thomas

2010-09-10

Plexins serve as receptors for semaphorins and play important roles in the developing nervous system. Plexin-B2 controls decisive developmental programs in the neural tube and cerebellum. However, whether Plexin-B2 also regulates biological functions in adult nonneuronal tissues is unknown. Here we show by two methodologically independent approaches that Plexin-B2 is expressed in discrete cell types of several nonneuronal tissues in the adult mouse. In the vasculature, Plexin-B2 is selectively expressed in functionally specialized endothelial cells. In endocrine organs, Plexin-B2 localizes to the pancreatic islets of Langerhans and to both cortex and medulla of the adrenal gland. Plexin-B2 expression is also detected in certain types of immune and epithelial cells. In addition, we report on a systematic comparison of the expression patterns of Plexin-B2 and its ligand Sema4C, which show complementarity or overlap in some but not all tissues. Furthermore, we demonstrate that Plexin-B2 and its family member Plexin-B1 display largely nonredundant expression patterns. This work establishes Plexin-B2 and Sema4C as potential regulators of the vascular and endocrine system and provides an anatomical basis to understand the biological functions of this ligand-receptor pair. Copyright 2010 Elsevier Inc. All rights reserved.

US healthcare costs attributable to type A and type B influenza.

Science.gov (United States)

Yan, Songkai; Weycker, Derek; Sokolowski, Stefania

2017-09-02

While the overall healthcare burden of seasonal influenza in the United States (US) has been well characterized, the proportion of influenza burden attributable to type A and type B illness warrants further elucidation. The aim of this study was to estimate numbers of healthcare encounters and healthcare costs attributable to influenza viral strains A and B in the US during the 2001/2002 - 2008/2009 seasons. Healthcare encounters and costs in the US during the 2001/2002 - 2008/2009 seasons for influenza type A and influenza type B were estimated separately and collectively, by season and age group, based on data from published literature and secondary sources for: rates of influenza-related encounters requiring formal healthcare, unit costs of influenza-related healthcare encounters, and estimates of population size. Across 8 seasons, projected annual numbers of influenza-related healthcare encounters ranged from 11.3-25.6 million, and healthcare costs, from $2.0-$5.8 billion. While the majority of influenza illness was attributable to type A strains, type B strains accounted for 37% of healthcare costs across all seasons, and as much as 66% in a single season. The outpatient burden of type B disease was considerable among persons aged 18-64 y while the hospital cost burden was highest in young children. Influenza viral strain B was associated with considerable health system burden each year during the period of interest. Increasing influenza vaccine coverage, especially with the recently approved quadrivalent products including an additional type B strain, could potentially reduce overall annual influenza burden in the US.

Involvement of mitogen-activated protein kinases and NFκB in LPS-induced CD40 expression on human monocytic cells

International Nuclear Information System (INIS)

Wu Weidong; Alexis, Neil E.; Chen Xian; Bromberg, Philip A.; Peden, David B.

2008-01-01

CD40 is a costimulatory molecule linking innate and adaptive immune responses to bacterial stimuli, as well as a critical regulator of functions of other costimulatory molecules. The mechanisms regulating lipopolysaccharide (LPS)-induced CD40 expression have not been adequately characterized in human monocytic cells. In this study we used a human monocytic cell line, THP-1, to investigate the possible mechanisms of CD40 expression following LPS exposure. Exposure to LPS resulted in a dose- and time-dependent increase in CD40 expression. Further studies using immunoblotting and pharmacological inhibitors revealed that mitogen-activated protein kinases (MAPKs) and NFκB were activated by LPS exposure and involved in LPS-induced CD40 expression. Activation of MAPKs was not responsible for LPS-induced NFκB activation. TLR4 was expressed on THP-1 cells and pretreatment of cells with a Toll-like receptor 4 (TLR4) neutralizing antibody (HTA125) significantly blunted LPS-induced MAPK and NFκB activation and ensuing CD40 expression. Additional studies with murine macrophages expressing wild type and mutated TLR4 showed that TLR4 was implicated in LPS-induced ERK and NFκB activation, and CD40 expression. Moreover, blockage of MAPK and NFκB activation inhibited LPS-induced TLR4 expression. In summary, LPS-induced CD40 expression in monocytic cells involves MAPKs and NFκB

Efficient inhibition of cathepsin B by a secreted type 1 cystatin of Fasciola gigantica.

Science.gov (United States)

Siricoon, Sinee; Grams, Suksiri Vichasri; Grams, Rudi

2012-12-01

Cysteine proteases are important antigens in the liver fluke genus Fasciola, essential for infection, protection and nutrition. While their biochemistry, biological roles and application as vaccines have been thoroughly studied there is a lack of data concerning their regulation. In the present study we have continued our investigation of cysteine protease inhibitors in Fasciola gigantica and demonstrate, in comparison with FgStefin-1 and human cystatin C, that a second type 1 cystatin of the parasite, FgStefin-2, has been evolutionary adapted to block cathepsin B. The protein, which unusually for a type 1 cystatin carries a signal peptide, is expressed from the metacercarial to adult stage and located in the epithelial cells of the intestinal tract in all stages and in the prostate gland cells in adults. Both cell types may contribute to the released FgStefin-2 observed in the ES product of the parasite. Distinct isoforms of cathepsin B are essential for host tissue penetration during the early infection process and FgStefin-2 may act as key regulator, required to protect the minute juvenile from autoproteolysis. Expression in the prostate gland in the adult stage suggests an additional regulative role of cysteine protease activity in the reproductive system. Copyright © 2012 Elsevier B.V. All rights reserved.

Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure.

Science.gov (United States)

Wu, Alan H B; Smith, Andrew

2004-03-15

B-type natriuretic peptide (BNP) and the inactive metabolite NT-proBNP are proven tests for diagnosis and staging of severity for patients with heart failure. However, the utility of these biomarkers for monitoring the success of drug therapy remains to be determined. Results of longitudinal studies on serial blood testing must be linked to overall patient morbidity and mortality outcomes. We previously determined the 8-week biological variability (BV) of BNP and NT-proBNP assays in healthy subjects and the 1-day BV for BNP alone in patients with compensated and stable heart failure. From these studies, the percent statistical change in serial samples of approximately 100% difference was estimated (95% confidence). We applied the biological variability concepts to the serial results of BNP and NT-proBNP collected from patients with heart failure and compared the performance of these two markers. While there are minor differences in the results between the assays from one time period to another, the overall interpretation of results are essentially identical. Moreover, the majority of individual serial time points are not significantly different from the previous value. Frequent testing (e.g. daily) for BNP and NT-proBNP to monitor therapy for patients with CHF is not indicated, as overall changes require several days to become evident.

The expression of GPR109A, NF-kB and IL-1β in peripheral blood leukocytes from patients with type 2 diabetes.

Science.gov (United States)

Liu, Fengxiu; Fu, Yucai; Wei, Chiju; Chen, Yongru; Ma, Shuhua; Xu, Wencan

2014-01-01

This study was designed to explore the association between the G protein-coupled receptor 109A (GPR109A) expression in peripheral blood leukocytes (PBLs) and type 2 diabetes (T2DM) and to discuss the regulation of inflammatory factors by GPR109A signaling. GPR109A signaling has been confirmed to be associated with homeostasis of glucose/lipid metabolism, but the role of signaling in T2DM is still poorly understood. Peripheral blood samples and biochemical data were collected from healthy individuals (normal controls) and T2DM patients. Immunocytochemical staining was used to detect the expression of GPR109A in PBLs. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure mRNA levels of GPR109A, NF-κB, and IL-1β in PBLs. Immunocytochemical staining showed that the GPR109A protein is localized in the nucleus and cytoplasm of granulocytes, monocytes, and lymphocytes. RT-PCR showed that mRNA levels of GPR109A, NF-κB, and IL-1β were higher in the T2DM group than in the control group (P<0.05). Correlation analysis showed a positive correlation both between GPR109A/NF-κB (r=0.376, P<0.05), and GPR109A/IL-1β (r=501, P<0.05) and between GPR109A and fasting plasma glucose (FPG) (r=0.179, P<0.05) and NF-κB /FPG (r=0.358, p<0.05). Our results suggest that GPR109A signaling is associated with T2DM, playing a role in regulation of the inflammatory cytokines. © 2014 by the Association of Clinical Scientists, Inc.

Changes in plasma atrial natriuretic factor in patients with idiopathic atrial fibrillation

International Nuclear Information System (INIS)

Du Tongxin; Xia Xiaojie; Qu Wei; Wang Shukui; Sun Junjiang

2002-01-01

To observe the changes in plasma atrial natriuretic factor (AFN) in patients with idiopathic atrial fibrillation and investigate its mechanism, plasma ANF, platelet count and hematocrit were detected in 21 cases with transient idiopathic atrial fibrillation (group A, A1 representing attack, while A2 termination), 28 with persistent idiopathic atrial fibrillation (group B), 27 suffered from rheumatic heart disease with mitral stenosis and persistent atrial fibrillation (group C), 32 with transient supraventricular tachycardia (group D) and 20 normal controls (group E). It was found that the level of ANF was significantly higher in patients with attacking transient idiopathic atrial fibrillation than that in group A2, D and E (P 0.05), while there was significant difference in hematocrit in group A1 compared with group A2, D, E (P < 0.01). It suggested that ANF and hematocrit play an important role in the attack of idiopathic atrial fibrillation

Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways

DEFF Research Database (Denmark)

Palsgaard, J.; Brøns, C.; Friedrichsen, M.

2009-01-01

BACKGROUND: Gene expression alterations have previously been associated with type 2 diabetes, however whether these changes are primary causes or secondary effects of type 2 diabetes is not known. As healthy first degree relatives of people with type 2 diabetes have an increased risk of developing...... type 2 diabetes, they provide a good model in the search for primary causes of the disease. METHODS/PRINCIPAL FINDINGS: We determined gene expression profiles in skeletal muscle biopsies from Caucasian males with type 2 diabetes, healthy first degree relatives, and healthy controls. Gene expression...... downregulated in people with type 2 diabetes. On the individual gene level, 11 genes showed altered expression levels in first degree relatives compared to controls, among others KIF1B and GDF8 (myostatin). LDHB was found to have a decreased expression in both groups compared to controls. CONCLUSIONS...

Use of biomarkers to guide outpatient therapy of heart failure.

Science.gov (United States)

DeBeradinis, Benedetta; Januzzi, James L

2012-11-01

Among patients with heart failure, concentrations of natriuretic peptides are strongly linked to the presence and severity of structural heart disease and are strongly prognostic in this setting. Additionally, favorable reduction in the concentration of either B-type natriuretic peptide (BNP) or B-type natriuretic peptide and its amino-terminal cleavage fragment (NT-proBNP) may be seen during treatment of heart failure, with parallel improvement in prognosis. This has led to the hypothesis that intensified treatment directed at reducing natriuretic peptide concentrations may improve outcomes in heart failure. In chronic heart failure, studies suggest that a strategy of standard-of-care management together with a goal to suppress BNP or NT-proBNP concentrations leads to greater application of guideline-derived medical therapy and is well tolerated. In certain studies of this BNP or NT-proBNP 'guided' approach, patients treated with biomarker-guided care had superior outcomes when compared with standard heart failure management alone, particularly in younger study populations, in patients with left ventricular systolic dysfunction, and particularly when substantial reductions in natriuretic peptides were achieved in association with biomarker-guided care. Natriuretic peptide 'guided' management appears promising in patients suffering from chronic heart failure. Large-scale pivotal trials to confirm the approach are planned.

Elevation of B-Type Natriuretic Peptide at Discharge is Associated With 2-Year Mortality After Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis: Insights From a Multicenter Prospective OCEAN-TAVI (Optimized Transcatheter Valvular Intervention-Transcatheter Aortic Valve Implantation) Registry.

Science.gov (United States)

Mizutani, Kazuki; Hara, Masahiko; Iwata, Shinichi; Murakami, Takashi; Shibata, Toshihiko; Yoshiyama, Minoru; Naganuma, Toru; Yamanaka, Futoshi; Higashimori, Akihiro; Tada, Norio; Takagi, Kensuke; Araki, Motoharu; Ueno, Hiroshi; Tabata, Minoru; Shirai, Shinichi; Watanabe, Yusuke; Yamamoto, Masanori; Hayashida, Kentaro

2017-07-14

In this study, we sought to investigate the 2-year prognostic impact of B-type natriuretic peptide (BNP) levels at discharge, following transcatheter aortic valve replacement. We enrolled 1094 consecutive patients who underwent transcatheter aortic valve replacement between 2013 and 2016. Study patients were stratified into 2 groups according to survival classification and regression tree analysis (high versus low BNP groups). We evaluated the impact of high BNP on 2-year mortality compared with that of low BNP using a multivariable Cox model, and assessed whether this stratification would improve predictive accuracy for determining 2-year mortality by assessing time-dependent net reclassification improvement and integrated discrimination improvement. The median age of patients was 85 years (quartile 82-88), and 29.2% of the study population were men. The median Society of Thoracic Surgeons score was 6.8 (4.7-9.5), and BNP at discharge was 186 (93-378) pg/mL. All-cause mortality following discharge was 7.9% (95% CI, 5.8-9.9%) at 1 year and 15.4% (95% CI, 11.6-19.0%) at 2 years. The survival classification and regression tree analysis revealed that the discriminating BNP level to discern 2-year mortality was 202 pg/mL, and that elevated BNP had a statistically significant impact on outcomes, with an adjusted hazard ratio of 2.28 (1.36-3.82, P =0.002). The time-dependent net reclassification improvement ( P =0.047) and integrated discrimination improvement ( P =0.029) analysis revealed that the incorporation of BNP stratification with other clinical variables significantly improved predictive accuracy for 2-year mortality. Elevation of BNP at discharge is associated with 2-year mortality after transcatheter aortic valve replacement. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Differential production of immunoglobulin classes and subclasses by mucosal-type human B-lymphocytes exposed in vitro to CpG oligodeoxynucleotides.

Science.gov (United States)

Cognasse, Fabrice; Acquart, Sophie; Beniguel, Lydie; Sabido, Odile; Chavarin, Patricia; Genin, Christian; Garraud, Olivier

2005-01-01

As B-lymphocytes play an important role in innate and adaptive immunity, we aimed to examine the effects of CpG oligodeoxynucleotides (ODNs) on purified tonsil-originating CD19+ B-cells, representing mucosal B-cells. We screened various K-type ODNs, reactive with human B-cells, and tested for the production of immunoglobulins in vitro. Using one CpG-ODN, DSP30, we observed that it could upregulate not only Toll-like receptor 9 (TLR9) mRNA expression in activated B-cells, but also the early expression of CD69 followed by the sequential expression of CD80, CD86 and the nuclear factor (NF)-kappaB pathway. Furthermore, mRNA expression of certain B-cell-derived cytokines was influenced by exposure to DSP30, with a strong upregulation of interleukin 6 (IL-6) and downregulation of IL1-beta. Stimulation of B-cells, co-stimulated with IL-2, IL-10 and soluble CD40 ligand (sCD40L) with different CpG-ODNs, had differing effects on the terminal differentiation in vitro of B-cells into immunoglobulin-secreting cells. TLR9 is involved in innate immunity and the recognition of bound CpG DNA from invading bacterial pathogens. As tonsillar B-cells are mucosal-type B-lymphocytes, this study suggests that CpG-ODNs show promise as mucosal adjuvants in modulating the local production of immunoglobulins of certain classes and subclasses, a crucial issue in vaccine perspectives.

Effects of telmisartan on the expression of NADPH oxidase subunits in the myocardium of type 2 diabetic rats

Directory of Open Access Journals (Sweden)

Jia-wei LI

2011-10-01

Full Text Available Objective To explore the effect of telmisartan on the expression of NADPH oxidase subunits p22phox and NOX4 in the myocardiam of type 2 diabetic rats.Methods Thirty-six male Wistar rats were randomly divided into two groups: normal control group(group A,n=10,diabetic model group(n=26.Type 2 diabetic model was established by high-fat and high-sugar diet followed by intraperitoneal injection of a low dose of streptozotocin(STZ.After the model was reproduced successfully,20 diabetic rats were randomly divided into diabetic subgroup(group B,n=10 and telmisartan-treated subgroup(group C,n=10.Rats in group C were orally administered telmisartan(5mg/kg/d,and rats in group A and B were given equivalent volume of normal saline.All rats were sacrificed 12 weeks after treatment.The mRNA expressions of myocardial p22phox and NOX4 were detected by real-time fluorescence quantitative PCR,and the protein expressions of myocardial connective tissue growth factor(CTGF and copper-zinc-superoxide dismutase(Cu-Zn-SOD were detected by immunohistochemical staining.Results Compared with group A,the ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF increased significantly in group B,and the protein expression of myocardial Cu-Zn-SOD decreased significantly(P 0.05.Conclusions Telmisartan can down-regulate the over-expression of myocardial NOX4 and p22phox mRNA in type 2 diabetic rats,lessen the myocardial damage induced by oxidative stress,thus plays a protective role in the myocardium of diabetic rats.

Does the natriuretic peptide system exist throughout the animal and plant kingdom?

Science.gov (United States)

Takei, Y

2001-06-01

Natriuretic peptides (NPs) and their receptors have been identified in vertebrate species ranging from elasmobranchs to mammals. Atrial, brain and ventricular NP (ANP, BNP and VNP) are endocrine hormones secreted from the heart, while C-type NP (CNP) is principally a paracrine factor in the brain and periphery. In elasmobranchs, only CNP is present in the heart and brain and it functions as a circulating hormone as well as a paracrine factor. Four types of NP receptors are cloned in vertebrates. NPR-A and NPR-B are guanylyl cyclase-coupled receptors, whereas NPR-C and NPR-D have only a short cytoplasmic domain. NPs are hormones important for volume regulation in mammals, while they act more specifically for Na(+) regulation in fishes. The presence of NP and its receptor has also been suggested in the most primitive vertebrate group, cyclostomes, and its molecular identification is in progress. The presence of ANP or its mRNA has been reported in the hearts and ganglia of various invertebrate species such as mollusks and arthropods using either antisera raised against mammalian ANP or rat ANP cDNA as probes. Immunoreactive ANP has also been detected in the unicellular Paramecium and in various species of plants including Metasequoia. Furthermore, the N-terminal prosegments of ANP, whose sequences are scarcely conserved even in vertebrates, have also been detected by the radioimmunoassay for human ANP prosegments in all invertebrate and plant species examined including Paramecium. Although these data are highly attractive, the current evidence is too circumstantial to be convincing that the immunoreactivity truly originates from ANP and its prosegments in such diverse organisms. The caution that has to be exercised in identification of vertebrate hormones from phylogenetically distant organisms is discussed.

Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko

2015-12-23

Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

Low Constitutive Cell Surface Expression of HLA-B Is Caused by a Posttranslational Mechanism Involving Glu180 and Arg239

DEFF Research Database (Denmark)

Dellgren, Christoffer; Ekwelum, Vanessa A. C.; Ormhøj, Maria

2016-01-01

HLA class I cell surface expression is crucial for normal immune responses, and variability in HLA expression may influence the course of infections. We have previously shown that classical HLA class I expression on many human cell types is biased with greatly reduced expression of HLA-B compared...... by affecting HLA processing in the Ag presentation pathway....

Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression

Directory of Open Access Journals (Sweden)

Juan Du

2018-04-01

Full Text Available Andrographolide (ANDRO has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains were subjected to 3 and 21% of O2 for various times (0–12 h to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.

Liver cancer: expression features of hepatitis B antigens

Directory of Open Access Journals (Sweden)

V. A. Tumanskiy

2013-12-01

Full Text Available Introduction. Hepatocellular carcinoma (HCC is currently the fifth most common malignancy in men and the eighth in women worldwide. According to the latest European Union countries’ statistics the incidence of HC cancer is about 8,29 per 100000 accidents, cholangiocellular (CC cancer – 0,9-1,3 per 100 thousand of population per year[10,14]. Hepatitis B virus (HBV is the major etiologic factor for the development of HCC [18]. People chronically infected with HBV are 20 times more likely to develop liver cancer than uninfected people [1,22,28]. Many studies have shown the association between Hepatitis B virus (HBV and hepatitis C virus (HCV infections and the development of cholangiocarcinoma (CCA [4,6,9,11,12]. At the same time, the expression features of HBsAg, HBcAg in HCC and CCA have not been studied clearly yet. Aim of investigation: to study the expression features of hepatitis B antigens in tumor tissue from patients with hepatocellular carcinoma and cholangiocarcinoma. Materials and methods. The complex pathomorphological research was performed using liver biopsies of 87 patients aged from 33 up to 83 years, where 50 (57,47% of them had HCC carcinoma and 37 (42,53% had cholangiocellular cancer. 15 patients among examined 87 ones were ill with chronic viral hepatitis (11 were ill with HCV, 3 – HBV B, 1 – HBV + HCV before, 72 cancer patients, corresponding to the clinical data, never had this one in their past medical history. The localization of hepatitis B surface antigen (HBsAg and core antigen (HBcAg was investigated by an indirect immunoperoxidase method in formalin-fixed, paraffin-embedded liver specimens obtained from 50 (57,47% patients with hepatocellular carcinoma and 37 (42,53% patients with cholangiocarcinoma. using antibodies Rb a-Hu Primary Hepatitis B Virus Core Antigen (HBcAg and Mo a-Hu Primary Hepatitis B Virus Surface Antigen (HBsAg, Сlone 3E7, and visualization system DAKO EnVision+ with diaminobenzidine. Liver

Moderne behandling af type B-aortadissektion

DEFF Research Database (Denmark)

Klitfod, L.; Baekgaard, N.; Just, S.

2008-01-01

Rapid classification is essential in the management of aortic dissections, as Type A dissections require surgery, while the optimal treatment of Type B dissections is controversial. Medical treatment with antihypertensive medication and analgesics has so far been the main treatment of uncomplicated...... Type B dissections, while surgery has been reserved for complications and persistent pain in spite of medical treatment. Endovascular techniques are less invasive than open repair and show promising early results Udgivelsesdato: 2008/9/8...

[Modern treatment of type B dissections

DEFF Research Database (Denmark)

Klitfod, L.; Baekgaard, N.; Just, S.

2008-01-01

Rapid classification is essential in the management of aortic dissections, as Type A dissections require surgery, while the optimal treatment of Type B dissections is controversial. Medical treatment with antihypertensive medication and analgesics has so far been the main treatment of uncomplicated...... Type B dissections, while surgery has been reserved for complications and persistent pain in spite of medical treatment. Endovascular techniques are less invasive than open repair and show promising early results Udgivelsesdato: 2008/9/8...

Human B cells fail to secrete type I interferons upon cytoplasmic DNA exposure.

Science.gov (United States)

Gram, Anna M; Sun, Chenglong; Landman, Sanne L; Oosenbrug, Timo; Koppejan, Hester J; Kwakkenbos, Mark J; Hoeben, Rob C; Paludan, Søren R; Ressing, Maaike E

2017-11-01

Most cells are believed to be capable of producing type I interferons (IFN I) as part of an innate immune response against, for instance, viral infections. In macrophages, IFN I is potently induced upon cytoplasmic exposure to foreign nucleic acids. Infection of these cells with herpesviruses leads to triggering of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP (cGAMP) synthase (cGAS). Thereby, the stimulator of interferon genes (STING) and the downstream molecules TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) are sequentially activated culminating in IFN I secretion. Human gamma-herpesviruses, such as Epstein-Barr virus (EBV), exploit B cells as a reservoir for persistent infection. In this study, we investigated whether human B cells, similar to macrophages, engage the cytoplasmic DNA sensing pathway to induce an innate immune response. We found that the B cells fail to secrete IFN I upon cytoplasmic DNA exposure, although they express the DNA sensors cGAS and IFI16 and the signaling components TBK1 and IRF3. In primary human B lymphocytes and EBV-negative B cell lines, this deficiency is explained by a lack of detectable levels of the central adaptor protein STING. In contrast, EBV-transformed B cell lines did express STING, yet both these lines as well as STING-reconstituted EBV-negative B cells did not produce IFN I upon dsDNA or cGAMP stimulation. Our combined data show that the cytoplasmic DNA sensing pathway is dysfunctional in human B cells. This exemplifies that certain cell types cannot induce IFN I in response to cytoplasmic DNA exposure providing a potential niche for viral persistence. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The expression of nifB gene from Herbaspirillum seropedicae is dependent upon the NifA and RpoN proteins.

Science.gov (United States)

Rego, Fabiane G M; Pedrosa, Fábio O; Chubatsu, Leda S; Yates, M Geoffrey; Wassem, Roseli; Steffens, Maria B R; Rigo, Liu U; Souza, Emanuel M

2006-12-01

The putative nifB promoter region of Herbaspirillum seropedicae contained two sequences homologous to NifA-binding site and a -24/-12 type promoter. A nifB::lacZ fusion was assayed in the backgrounds of both Escherichia coli and H. seropedicae. In E. coli, the expression of nifB::lacZ occurred only in the presence of functional rpoN and Klebsiella pneumoniae nifA genes. In addition, the integration host factor (IHF) stimulated the expression of the nifB::lacZ fusion in this background. In H. seropedicae, nifB expression occurred only in the absence of ammonium and under low levels of oxygen, and it was shown to be strictly dependent on NifA. DNA band shift experiments showed that purified K. pneumoniae RpoN and E. coli IHF proteins were capable of binding to the nifB promoter region, and in vivo dimethylsulfate footprinting showed that NifA binds to both NifA-binding sites. These results strongly suggest that the expression of the nifB promoter of H. seropedicae is dependent on the NifA and RpoN proteins and that the IHF protein stimulates NifA activation of nifB promoter.

Extinct type of human parvovirus B19 persists in tonsillar B cells

OpenAIRE

Pyöriä, Lari; Toppinen, Mari; Mantyla, Elina; Hedman, Lea; Aaltonen, Leena-Maija; Vihinen-Ranta, Maija; Ilmarinen, Taru; Soderlund-Venermo, Maria; Hedman, Klaus; Perdomo, Maria

2017-01-01

Parvovirus B19 (B19V) DNA persists lifelong in human tissues, but the cell type harbouring it remains unclear. We here explore B19V DNA distribution in B, T and monocyte cell lineages of recently excised tonsillar tissues from 77 individuals with an age range of 2?69 years. We show that B19V DNA is most frequent and abundant among B cells, and within them we find a B19V genotype that vanished from circulation >40 years ago. Since re-infection or re-activation are unlikely with this virus type...

Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers.

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Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin

2017-07-01

Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3+/TrkB- fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways. Copyright © 2017. Published by Elsevier Inc.

EphrinB1 expression is dysregulated and promotes oncogenic signaling in medulloblastoma.

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McKinney, Nicole; Yuan, Liangping; Zhang, Hongying; Liu, Jingbo; Cho, Yoon-Jae; Rushing, Elisabeth; Schniederjan, Matthew; MacDonald, Tobey J

2015-01-01

Eph receptors and ephrin ligands are master regulators of oncogenic signaling required for proliferation, migration, and metastasis. Yet, Eph/ephrin expression and activity in medulloblastoma (MB), the most common malignant brain tumor of childhood, remains poorly defined. We hypothesized that Eph/ephrins are differentially expressed by sonic hedgehog (SHH) and non-SHH MB and that specific members contribute to the aggressive phenotype. Affymetrix gene expression profiling of 29 childhood MB, separated into SHH (N = 11) and non-SHH (N = 18), was performed followed by protein validation of selected Eph/ephrins in another 60 MB and two MB cell lines (DAOY, D556). Functional assays were performed using MB cells overexpressing or deleted for selected ephrins. We found EPHB4 and EFNA4 almost exclusively expressed by SHH MB, whereas EPHA2, EPHA8, EFNA1 and EFNA3 are predominantly expressed by non-SHH MB. The remaining family members, except EFNB1, are ubiquitously expressed by over 70-90 % MB, irrespective of subgroup. EFNB1 is the only member differentially expressed by 28 % of SHH and non-SHH MB. Corresponding protein expression for EphB/ephrinB1 and B2 was validated in MB. Only ephrinB2 was also detected in fetal cerebellum, indicating that EphB/ephrinB1 expression is MB-specific. EphrinB1 immunopositivity localizes to tumor cells within MB with the highest proliferative index. EphrinB1 overexpression promotes EphB activation, alters F-actin distribution and morphology, decreases adhesion, and significantly promotes proliferation. Either silencing or overexpression of ephrinB1 impairs migration. These results indicate that EphrinB1 is uniquely dysregulated in MB and promotes oncogenic responses in MB cells, implicating ephrinB1 as a potential target.

NF-kappaB mediates FGF signal regulation of msx-1 expression.

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Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

2001-09-01

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas.

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He, Miaoxia; Chen, Keting; Li, Suhong; Zhang, Shimin; Zheng, Jianming; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin

2016-01-01

Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better

Biomarker Guided Therapy in Chronic Heart Failure

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Bektas, Sema

2015-01-01

This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

Prognostic value of N-terminal prohormone brain natriuretic peptide for in-hospital and long-term outcomes in patients with infective endocarditis.

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Wei, Xue-Biao; Liu, Yuan-Hui; He, Peng-Cheng; Yu, Dan-Qing; Zhou, Ying-Ling; Tan, Ning; Chen, Ji-Yan

2017-05-01

Background Limited research studies with a large sample size were performed to evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for in-hospital or long-term poor outcomes in patients with infective endocarditis. Methods A total of 703 patients with infective endocarditis were enrolled and divided into four groups according to admission NT-pro-BNP (pg/mL) quartiles: Q1 (3522). Multivariate regression was used to determine independent risk of NT-proBNP for in-hospital and one-year death. Results In-hospital death occurred in 9.0% of patients. The in-hospital mortality was increased from the lowest to the highest NT-proBNP quartiles (1.1%, 3.4%, 9.1% and 22.3%, P  2260 pg/mL had 76.2% sensitivity and 69.1% specificity for predicting in-hospital death. Kaplan-Meier analysis showed that patients with NT-proBNP > 2260 pg/ml had a worse prognosis than those without (log-rank test 18.84, P endocarditis.

Deletion of the B-B' and C-C' regions of inverted terminal repeats reduces rAAV productivity but increases transgene expression.

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Zhou, Qingzhang; Tian, Wenhong; Liu, Chunguo; Lian, Zhonghui; Dong, Xiaoyan; Wu, Xiaobing

2017-07-14

Inverted terminal repeats (ITRs) of the adeno-associated virus (AAV) are essential for rescue, replication, packaging, and integration of the viral genome. While ITR mutations have been identified in previous reports, we designed a new truncated ITR lacking the B-B' and C-C' regions named as ITRΔBC and investigated its effects on viral genome replication, packaging, and expression of recombinant AAV (rAAV). The packaging ability was compared between ITRΔBC rAAV and wild-type (wt) ITR rAAV. Our results showed the productivity of ITRΔBC rAAV was reduced 4-fold, which is consistent with the 8-fold decrease in the replication of viral genomic DNA of ITRΔBC rAAV compared with wt ITR rAAV. Surprisingly, transgene expression was significantly higher for ITRΔBC rAAV. A preliminary exploration of the underlying mechanisms was carried out by inhibiting and degrading the ataxia telangiectasia mutated (ATM) protein and the Mre11 complex (MRN), respectively, since the rAAV expression was inhibited by the ATM and/or MRN through cis interaction or binding with wt ITRs. We demonstrated that the inhibitory effects were weakened on ITRΔBC rAAV expression. This study suggests deletion in ITR can affect the transgene expression of AAV, which provides a new way to improve the AAV expression through ITRs modification.

Angiotensin II modulates interleukin-1β-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-κB crosstalk

International Nuclear Information System (INIS)

Xu, Shanqin; Zhi, Hui; Hou, Xiuyun; Jiang, Bingbing

2011-01-01

Highlights: → We examine how angiotensin II modulates ERK-NF-κB crosstalk and gene expression. → Angiotensin II suppresses IL-1β-induced prolonged ERK and NF-κB activation. → ERK-RSK1 signaling is required for IL-1β-induced prolonged NF-κB activation. → Angiotensin II modulates NF-κB responsive genes via regulating ERK-NF-κB crosstalk. → ERK-NF-κB crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. In cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1β-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-κB, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1β-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1β, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE -/- ) mice. VCAM-1 and iNOS expression were higher in ApoE -/- than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE -/- mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that angiotensin II can differentially modulate inflammatory gene expression in aortic smooth muscle cells

Parvovirus b19 DNA CpG dinucleotide methylation and epigenetic regulation of viral expression.

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Francesca Bonvicini

Full Text Available CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression.The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections.The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19.

Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

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Bonvicini, Francesca; Manaresi, Elisabetta; Di Furio, Francesca; De Falco, Luisa; Gallinella, Giorgio

2012-01-01

CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression. The analysis of CpG dinucleotide methylation of Parvovirus B19 DNA was carried out by an aptly designed quantitative real-time PCR assay on bisulfite-modified DNA. The effects of CpG methylation on the regulation of viral genome expression were first investigated by transfection of either unmethylated or in vitro methylated viral DNA in a model cell line, showing that methylation of viral DNA was correlated to lower expression levels of the viral genome. Then, in the course of in vitro infections in different cellular environments, it was observed that absence of viral expression and genome replication were both correlated to increasing levels of CpG methylation of viral DNA. Finally, the presence of CpG methylation was documented in viral DNA present in bioptic samples, indicating the occurrence and a possible role of this epigenetic modification in the course of natural infections. The presence of an epigenetic level of regulation of viral genome expression, possibly correlated to the silencing of the viral genome and contributing to the maintenance of the virus in tissues, can be relevant to the balance and outcome of the different types of infection associated to Parvovirus B19. PMID:22413013

27-Oxygenated cholesterol induces expression of CXCL8 in macrophages via NF-κB and CD88

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Kim, Sun-Mi, E-mail: lala1647@hanmail.net [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Chung Won, E-mail: vasculardoctorlee@gmail.com [Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Pusan 602-739 (Korea, Republic of); Kim, Bo-Young, E-mail: kimboyoung@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Jung, Young-Suk, E-mail: youngjung@pusan.ac.kr [College of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Eo, Seong-Kug, E-mail: vetvirus@chonbuk.ac.kr [College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan, Jeonbuk 570-752 (Korea, Republic of); Park, Young Chul, E-mail: ycpark@pusan.ac.kr [Department of Microbiology & Immunology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Kim, Koanhoi, E-mail: koanhoi@pusan.ac.kr [Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870 (Korea, Republic of)

2015-08-07

We attempted to determine the effects of a milieu rich in cholesterol molecules on expression of chemokine CXCL8. A high-cholesterol diet led to an increased transcription of the IL-8 gene in the arteries and elevated levels of CXCL8 in sera of ApoE{sup −/−} mice, compared with those of wild-type C57BL/6 mice. Treatment of THP-1 monocyte/macrophage cells with 27-hydroxycholesterol (27OHChol) resulted in transcription of the IL-8 gene and increased secretion of its corresponding gene product whereas cholesterol did not induce expression of CXCL8 in THP-1 cells. 27OHChol-induced transcription of the IL-8 gene was blocked by cycloheximide, but not by polymyxin B. Treatment of THP-1 cells with 27OHChol caused translocation of p65 NF-κB subunit into the nucleus and up-regulation of CD88. Inhibition of NF-κB and CD88 using SN50 and W-54011, respectively, resulted in reduced transcription of the IL-8 gene and attenuated secretion of CXCL8 induced by 27OHChol. We propose that oxidatively modified cholesterol like 27OHChol, rather than cholesterol, is responsible for sustained expression of CXCL8 in monocytes/macrophages in atherosclerotic arteries. - Highlights: • Consumption of a high-cholesterol diet leads to increased CXCL8 expression in ApoE{sup −/−} mice. • 27OHChol, but not cholesterol, up-regulates expression of CXCL8 in macrophages. • 27OHChol enhances nuclear translocation of NF-κB and expression of CD88 in macrophages. • Inhibition of NF-κB or CD88 results in decreased CXCL8 expression induced by 27OHChol. • 27OHChol up-regulates CXCL8 expression via NF-κB and CD88 in macrophages.

Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.

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Lin, Xue; Yang, Penghua; Reece, E Albert; Yang, Peixin

2017-08-01

Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The type 2 diabetes mellitus embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, desmin, and adrenomedullin. Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor, osteopontin, and galectin-3 genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic group. Maternal diabetes significantly increased β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and desmin expression, but decreased expression of adrenomedullin. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type 2 diabetes mellitus

Study of the Expression of Survivin & Its Splice Variants; ΔEx3, 2b and 3b as Diagnostic Molecular Markers in Breast Cancer

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E Babaei

2009-07-01

Full Text Available Introduction: Survivin is a new member of the Inhibitor Apotosis Protein family (IAP which plays an important role in the regulation of both cell cycle and apoptosis. Its distinct expression in tumor cells as compared to normal adult cells introduces Survivin as the fourth transcriptom demonstrated in tumors. Breast cancer is the most common malignancy among women and scientist`s efforts to classify it has lead to various molecular subtypes and controversial results. Because of the high prevalence of these tumors and lack of suitable molecular markers for diagnosis and prognosis, there are ongoing efforts to find molecular markers which can distinguish nontumoral from tumor tissues. In this study we evaluate the potential usefulness of Survivin and its splice variants ΔEx3, 2b and 3b as molecular markers in breast cancer. Methods: We studied 18 tumor and 17 non tumor adjacent tissues. Transcription levels were measured by Semiquantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR and normalized by ß2m as an internal control. Results: 1Survivin and its splice variants; Δex3, 2b and 3b showed differentially higher expression levels in tumors than adjacent normal tissues. 2 The expression levels of Survivin, Survivin-ΔEx3 and Survivin-3b were significantly correlated with the type of tumors. 3 Survivin-2b was expressed in a few samples. 4 Survivin-3b was detected only in tumor samples. Also, our results showed that ΔEx3 variant can be introduced as a dominant expressed variant in breast cancer. Conclusion: Our data indicated that the expression of Survivin, Survivin ∆Ex3 and especially, Survivin-3b were correlated with cancerous nature of tumors and Survivin-∆Ex3 was the most common expressed variant in breast carcinomas. These results besides confirming the potential usefulness of Survivin and its splice variants as molecular markers in breast cancer, demonstrated the role of the gene and its splice variants, especially 3b

Nanoparticle-Based Delivery of Anaplasma marginale Membrane Proteins; VirB9-1 and VirB10 Produced in the Pichia pastoris Expression System.

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Zhang, Bing; Cavallaro, Antonio S; Mody, Karishma T; Zhang, Jun; Deringer, James R; Brown, Wendy C; Mahony, Timothy J; Yu, Chengzhong; Mitter, Neena

2016-11-05

Bovine anaplasmosis or cattle-tick fever is a tick-borne haemolytic disease caused by the rickettsial haemoparasite Anaplasma marginale in tropical and subtropical areas of the world. While difficult to express, the proteins VirB9-1 and VirB10 are immunogenic components of the outer membrane type IV secretion system that have been identified as candidate antigens for vaccines targeting of A. marginale . Soluble VirB9-1 and VirB10 were successfully expressed using Pichia pastoris . When formulated with the self-adjuvanting silica vesicles, SV-100 (diameter: 50 nm, and pore entrance size: 6 nm), 200 µg of VirB9-1 and VirB10 were adsorbed per milligram of nanoparticle. The VirB9-1 and VirB10, SV-100 formulations were shown to induce higher antibody responses in mice compared to the QuilA formulations. Moreover, intracellular staining of selected cytokines demonstrated that both VirB9-1 and VirB10 formulations induced cell-mediated immune responses in mice. Importantly, the SV-100 VirB9-1 and VirB10 complexes were shown to specifically stimulate bovine T-cell linages derived from calves immunised with A. marginale outer membrane fractions, suggesting formulations will be useful for bovine immunisation and protection studies. Overall this study demonstrates the potential of self-adjuvanting silica vesicle formulations to address current deficiencies in vaccine delivery applications.

Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

International Nuclear Information System (INIS)

Zhou, Heng; Guo, Wei; Long, Cong; Wang, Huan; Wang, Jingchao; Sun, Xiaoping

2015-01-01

Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression

Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

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Zhou, Heng [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Long, Cong; Wang, Huan; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

2015-01-16

Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.

Low PIP4K2B expression in human breast tumors correlates with reduced patient survival: A role for PIP4K2B in the regulation of E-cadherin expression.

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Keune, Willem-Jan; Sims, Andrew H; Jones, David R; Bultsma, Yvette; Lynch, James T; Jirström, Karin; Landberg, Goran; Divecha, Nullin

2013-12-01

Phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase β (PIP4K2B) directly regulates the levels of two important phosphoinositide second messengers, PtdIns5P and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2]. PIP4K2B has been linked to the regulation of gene transcription, to TP53 and AKT activation, and to the regulation of cellular reactive oxygen accumulation. However, its role in human tumor development and on patient survival is not known. Here, we have interrogated the expression of PIP4K2B in a cohort (489) of patients with breast tumor using immunohistochemical staining and by a meta-analysis of gene expression profiles from 2,999 breast tumors, both with associated clinical outcome data. Low PIP4K2B expression was associated with increased tumor size, high Nottingham histological grade, Ki67 expression, and distant metastasis, whereas high PIP4K2B expression strongly associated with ERBB2 expression. Kaplan-Meier curves showed that both high and low PIP4K2B expression correlated with poorer patient survival compared with intermediate expression. In normal (MCF10A) and tumor (MCF7) breast epithelial cell lines, mimicking low PIP4K2B expression, using short hairpin RNA interference-mediated knockdown, led to a decrease in the transcription and expression of the tumor suppressor protein E-cadherin (CDH1). In MCF10A cells, knockdown of PIP4K2B enhanced TGF-β-induced epithelial to mesenchymal transition (EMT), a process required during the development of metastasis. Analysis of gene expression datasets confirmed the association between low PIP4K2B and low CDH1expression. Decreased CDH1 expression and enhancement of TGF-β-induced EMT by reduced PIP4K2B expression might, in part, explain the association between low PIP4K2B expression and poor patient survival.

IL-15 expression on RA synovial fibroblasts promotes B cell survival.

Directory of Open Access Journals (Sweden)

Marta Benito-Miguel

Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

Adult-type hypolactasia and regulation of lactase expression

DEFF Research Database (Denmark)

Troelsen, Jesper Thorvald

2005-01-01

, the main carbohydrate in milk. Individuals with adult-type hypolactasia lose their lactase expression before adulthood and consequently often become lactose intolerant with associated digestive problems (e.g. diarrhoea). In contrast, lactase persistent individuals have a lifelong lactase expression......A common genetically determined polymorphism in the human population leads to two distinct phenotypes in adults, lactase persistence and adult-type hypolactasia (lactase non-persistence). All healthy newborn children express high levels of lactase and are able to digest large quantities of lactose...... and are able to digest lactose as adults. Lactase persistence can be regarded as the mutant phenotype since other mammals down-regulate their lactase expression after weaning (the postweaning decline). This phenomenon does not occur in lactase persistent individuals. The regulation of lactase expression...

Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

International Nuclear Information System (INIS)

Leitman, D.C.

1988-01-01

The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using 125 I-ANP 8-33 . Specific 125 I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells.

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Huang, Yu-Hsuan; Tsai, Kevin; Tan, Sara Y; Kang, Sohyeong; Ford, Mandy L; Harder, Kenneth W; Priatel, John J

2017-01-01

Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8 + T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a - / - CD8 + T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a - / - CD8 + T cells responded equivalently to wild-type CD8 + T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8 + T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8 + T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8 + T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas.

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells

Science.gov (United States)

2017-01-01

ABSTRACT Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein–Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8+ T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a−/− CD8+ T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a−/− CD8+ T cells responded equivalently to wild-type CD8+ T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8+ T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8+ T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8+ T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas. PMID:28344876

A gain-of-function mutation in Tnni2 impeded bone development through increasing Hif3a expression in DA2B mice.

Directory of Open Access Journals (Sweden)

Xiaoquan Zhu

2014-10-01

Full Text Available Distal arthrogryposis type 2B (DA2B is an important genetic disorder in humans. However, the mechanisms governing this disease are not clearly understood. In this study, we generated knock-in mice carrying a DA2B mutation (K175del in troponin I type 2 (skeletal, fast (TNNI2, which encodes a fast-twitch skeletal muscle protein. Tnni2K175del mice (referred to as DA2B mice showed typical DA2B phenotypes, including limb abnormality and small body size. However, the current knowledge concerning TNNI2 could not explain the small body phenotype of DA2B mice. We found that Tnni2 was expressed in the osteoblasts and chondrocytes of long bone growth plates. Expression profile analysis using radii and ulnae demonstrated that Hif3a expression was significantly increased in the Tnni2K175del mice. Chromatin immunoprecipitation assays indicated that both wild-type and mutant tnni2 protein can bind to the Hif3a promoter using mouse primary osteoblasts. Moreover, we showed that the mutant tnni2 protein had a higher capacity to transactivate Hif3a than the wild-type protein. The increased amount of hif3a resulted in impairment of angiogenesis, delay in endochondral ossification, and decrease in chondrocyte differentiation and osteoblast proliferation, suggesting that hif3a counteracted hif1a-induced Vegf expression in DA2B mice. Together, our data indicated that Tnni2K175del mutation led to abnormally increased hif3a and decreased vegf in bone, which explain, at least in part, the small body size of Tnni2K175del mice. Furthermore, our findings revealed a new function of tnni2 in the regulation of bone development, and the study of gain-of-function mutation in Tnni2 in transgenic mice opens a new avenue to understand the pathological mechanism of human DA2B disorder.

Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice

International Nuclear Information System (INIS)

Hufbauer, M.; Lazic, D.; Akguel, B.; Brandsma, J.L.; Pfister, H.; Weissenborn, S.J.

2010-01-01

Human papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3 weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2 days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis.

Isolation, molecular cloning and expression of cellobiohydrolase B (CbhB) from Aspergillus niger in Escherichia coli

International Nuclear Information System (INIS)

Woon, J. S. K.; Murad, A. M. A.; Abu Bakar, F. D.

2015-01-01

A cellobiohydrolase B (CbhB) from Aspergillus niger ATCC 10574 was cloned and expressed in E. coli. CbhB has an open reading frame of 1611 bp encoding a putative polypeptide of 536 amino acids. Analysis of the encoded polypeptide predicted a molecular mass of 56.2 kDa, a cellulose binding module (CBM) and a catalytic module. In order to obtain the mRNA of cbhB, total RNA was extracted from A. niger cells induced by 1% Avicel. First strand cDNA was synthesized from total RNA via reverse transcription. The full length cDNA of cbhB was amplified by PCR and cloned into the cloning vector, pGEM-T Easy. A comparison between genomic DNA and cDNA sequences of cbhB revealed that the gene is intronless. Upon the removal of the signal peptide, the cDNA of cbhB was cloned into the expression vector pET-32b. However, the recombinant CbhB was expressed in Escherichia coli Origami DE3 as an insoluble protein. A homology model of CbhB predicted the presence of nine disulfide bonds in the protein structure which may have contributed to the improper folding of the protein and thus, resulting in inclusion bodies in E. coli

Isolation, molecular cloning and expression of cellobiohydrolase B (CbhB) from Aspergillus niger in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Woon, J. S. K., E-mail: jameswoon@siswa.ukm.edu.my; Murad, A. M. A., E-mail: munir@ukm.edu.my; Abu Bakar, F. D., E-mail: fabyff@ukm.edu.my [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor (Malaysia)

2015-09-25

A cellobiohydrolase B (CbhB) from Aspergillus niger ATCC 10574 was cloned and expressed in E. coli. CbhB has an open reading frame of 1611 bp encoding a putative polypeptide of 536 amino acids. Analysis of the encoded polypeptide predicted a molecular mass of 56.2 kDa, a cellulose binding module (CBM) and a catalytic module. In order to obtain the mRNA of cbhB, total RNA was extracted from A. niger cells induced by 1% Avicel. First strand cDNA was synthesized from total RNA via reverse transcription. The full length cDNA of cbhB was amplified by PCR and cloned into the cloning vector, pGEM-T Easy. A comparison between genomic DNA and cDNA sequences of cbhB revealed that the gene is intronless. Upon the removal of the signal peptide, the cDNA of cbhB was cloned into the expression vector pET-32b. However, the recombinant CbhB was expressed in Escherichia coli Origami DE3 as an insoluble protein. A homology model of CbhB predicted the presence of nine disulfide bonds in the protein structure which may have contributed to the improper folding of the protein and thus, resulting in inclusion bodies in E. coli.

Isolation, molecular cloning and expression of cellobiohydrolase B (CbhB) from Aspergillus niger in Escherichia coli

Science.gov (United States)

Woon, J. S. K.; Murad, A. M. A.; Abu Bakar, F. D.

2015-09-01

A cellobiohydrolase B (CbhB) from Aspergillus niger ATCC 10574 was cloned and expressed in E. coli. CbhB has an open reading frame of 1611 bp encoding a putative polypeptide of 536 amino acids. Analysis of the encoded polypeptide predicted a molecular mass of 56.2 kDa, a cellulose binding module (CBM) and a catalytic module. In order to obtain the mRNA of cbhB, total RNA was extracted from A. niger cells induced by 1% Avicel. First strand cDNA was synthesized from total RNA via reverse transcription. The full length cDNA of cbhB was amplified by PCR and cloned into the cloning vector, pGEM-T Easy. A comparison between genomic DNA and cDNA sequences of cbhB revealed that the gene is intronless. Upon the removal of the signal peptide, the cDNA of cbhB was cloned into the expression vector pET-32b. However, the recombinant CbhB was expressed in Escherichia coli Origami DE3 as an insoluble protein. A homology model of CbhB predicted the presence of nine disulfide bonds in the protein structure which may have contributed to the improper folding of the protein and thus, resulting in inclusion bodies in E. coli.

Brain natriuretic peptide and right heart dysfunction after heart transplantation.

Science.gov (United States)

Talha, Samy; Charloux, Anne; Piquard, François; Geny, Bernard

2017-06-01

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative proteome changes in Arabidopsis thaliana suspension-cultured cells in response to plant natriuretic peptides

KAUST Repository

Turek, Ilona; Wheeler, Janet I.; Gehring, Christoph A; Irving, Helen R.; Marondedze, Claudius

2015-01-01

Proteome changes in the Arabidopsis thaliana suspension cells in response to the A. thaliana plant natriuretic peptide (PNP), AtPNP-A (At2g18660) were assessed using quantitative proteomics employing tandem mass tag (TMT) labeling and tandem mass spectrometry (LC–MS/MS). In this study, we characterized temporal responses of suspension-cultured cells to 1 nM and 10 pM AtPNP-A at 0, 10 and 30 min post-treatment. Both concentrations we found to yield a distinct differential proteome signature. The data shown in this article are associated with the article “Plant natriuretic peptides induce a specific set of proteins diagnostic for an adaptive response to abiotic stress” by Turek et al. (Front. Plant Sci. 5 (2014) 661) and have been deposited to the ProteomeXchange with identifier PXD001386.

Quantitative proteome changes in Arabidopsis thaliana suspension-cultured cells in response to plant natriuretic peptides

KAUST Repository

Turek, Ilona

2015-06-30

Proteome changes in the Arabidopsis thaliana suspension cells in response to the A. thaliana plant natriuretic peptide (PNP), AtPNP-A (At2g18660) were assessed using quantitative proteomics employing tandem mass tag (TMT) labeling and tandem mass spectrometry (LC–MS/MS). In this study, we characterized temporal responses of suspension-cultured cells to 1 nM and 10 pM AtPNP-A at 0, 10 and 30 min post-treatment. Both concentrations we found to yield a distinct differential proteome signature. The data shown in this article are associated with the article “Plant natriuretic peptides induce a specific set of proteins diagnostic for an adaptive response to abiotic stress” by Turek et al. (Front. Plant Sci. 5 (2014) 661) and have been deposited to the ProteomeXchange with identifier PXD001386.

PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana.

Science.gov (United States)

Blenau, Wolfgang; Balfanz, Sabine; Baumann, Arnd

2017-10-30

The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP] i ) whereas type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . Here; we report that the American cockroach ( Periplaneta americana ) expresses a second type 1 tyramine receptor (PeaTAR1B) in addition to PeaTAR1A (previously called PeaTYR1). When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP] i . Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana ; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine.

PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana

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Wolfgang Blenau

2017-10-01

Full Text Available The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G protein-coupled receptors (GPCRs. Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP]i whereas type 2 tyramine receptors can mediate Ca2+ signals or both Ca2+ signals and effects on [cAMP]i. Here; we report that the American cockroach (Periplaneta americana expresses a second type 1 tyramine receptor (PeaTAR1B in addition to PeaTAR1A (previously called PeaTYR1. When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP]i. Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine.

Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity.

Science.gov (United States)

Kistorp, Caroline; Bliddal, Henning; Goetze, Jens P; Christensen, Robin; Faber, Jens

2014-01-01

Cardiac natriuretic peptides are established biomarkers in heart disease, but are also affected by body mass index (BMI). The purpose of the present study was to examine the impact of weight loss and changes in body composition following dietary intervention on plasma concentrations of the prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and adrenomedullin (proADM). A total of 52 healthy obese subjects, 47 women and 5 men (BMI 36.5 ± 5.6 kg/m(2)) were randomised to either an intensive weight reduction programme using a combination of very low calorie diet (810 kcal/day) and conventional hypo-energetic diet (1200 kcal/day) for 52 weeks, or to a control group that was offered diet-related counselling. N-terminal proBNP (NT-proBNP), mid-regional proANP (MR-proANP) and proADM (MR-proADM) and body composition using dual-energy x-ray absorptiometry (DEXA) scanning were determined at baseline and after 52 weeks. Comparisons between groups were analysed using t-tests. Changes from the baseline within the groups were analysed with paired tests. Changes in the variables, delta (∆), were calculated as 52 weeks minus the baseline. In the intervention group, BMI decreased by almost 20% (31.6 ± 6.2 vs. 37.1 ± 6.1 kg/m(2); P <0.001) with a loss of body fat of 23.5 ± 15.5% (P < 0.001). Plasma concentrations of NT-proBNP and MR-proANP increased (from 55 ± 31 to 97 ± 55 pg/ml; P < 0.001, and from 59 ± 21 to 74 ± 26 pmol/L; P < 0.001), whereas MR-proADM decreased (from 573 ± 153 to 534 ± 173 pmol/L; P <0.001). Changes (Δ) in MR-proANP correlated with Δfat mass (r = -0.359; P = 0.011) and Δglucose (r = -0.495; P <0.001), while increases in NT-proBNP were primarily associated with reduced plasma glucose (r = -0.462; P <0.001). A modest but significant weight loss of 6% (P < 0.001) was found in the control group with no changes in plasma concentrations of NT-proBNP or MR-proANP, and a minor change in MR-proADM. Plasma NT-proBNP and MR

Effects of phosphodiesterase inhibitors on atrial dynamics induced by C-type natriuretic peptide in isolated beating rabbit atria

International Nuclear Information System (INIS)

Ding Dazhi; Cui Xun; Jin Xiunan; Lan Ying; Liu Liping; Hong Lan

2010-01-01

Objective: To investigate the effects of phosphodiesterase inhibitors (PDEI) on atrial dynamics induced by C-type natriuretic peptide (CNP) and the contents of cyclic nucleotide (cAMP, cGMP) in isolated beating rabbit atria. Methods: After the rabbits had been anesthetized, the hearts were removed rapidly. The left auricles were isolated and fixed on the atrial perfusion system. The atrial stroke volume and the pulse pressure were observed by CNP with or without PDEIs pretreatment. The contents of cAMP and cGMP were measured by radioimmunoassay. Results: (1)Compared with control cycle group, CNP (30.0 nmol · L -1 ) obviously decreased the atrial stroke volume and pulse pressure (P 0.05). (2)Compared with control cycle group, IBMX(1000.0 nmol · L -1 ), a non-selective inhibitor of PDE, significantly increased the atrial stroke volume, pulse pressure, cAMP and cGMP contents (P -1 ) plus CNP (30.0 nmol · L -1 )group and IBMX group (P>0.05). (3)Compared with control cycle group, EHNA(30.0 nmol · L -1 ), an inhibitor of PDE2, obviously decreased the atrial stroke volume and pulse pressure (P 0.05). EHNA(30.0 nmol · L -1 ) plus CNP (30.0 nmol · L -1 ) showed similar roles with EHNA only. (4)Compared with control cycle group, milrinone (1.0 nmol · L -1 ), an inhibitor of PDE3, significantly increased the content of cAMP (P 0.05). CNP (30.0 nmol · L -1 ) obviously decreased the atrial stroke volume and pulse pressure (P 0.05). Conclusion: CNP can inhibit atrial dynamics by increasing the content of cGMP, the different inhibitors of PDEs play different roles in the CNP-induced inhibition of atrial dynamics in isolated beating rabbit atria. (authors)

Increased Cx32 expression in spinal cord TrkB oligodendrocytes following peripheral axon injury.

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Coulibaly, Aminata P; Isaacson, Lori G

2016-08-03

Following injury to motor axons in the periphery, retrograde influences from the injury site lead to glial cell plasticity in the vicinity of the injured neurons. Following the transection of peripherally located preganglionic axons of the cervical sympathetic trunk (CST), a population of oligodendrocyte (OL) lineage cells expressing full length TrkB, the cognate receptor for brain derived neurotrophic factor (BDNF), is significantly increased in number in the spinal cord. Such robust plasticity in OL lineage cells in the spinal cord following peripheral axon transection led to the hypothesis that the gap junction communication protein connexin 32 (Cx32), which is specific to OL lineage cells, was influenced by the injury. Following CST transection, Cx32 expression in the spinal cord intermediolateral cell column (IML), the location of the parent cell bodies, was significantly increased. The increased Cx32 expression was localized specifically to TrkB OLs in the IML, rather than other cell types in the OL cell lineage, with the population of Cx32/TrkB cells increased by 59%. Cx32 expression in association with OPCs was significantly decreased at one week following the injury. The results of this study provide evidence that peripheral axon injury can differentially affect the gap junction protein expression in OL lineage cells in the adult rat spinal cord. We conclude that the retrograde influences originating from the peripheral injury site elicit dramatic changes in the CNS expression of Cx32, which in turn may mediate the plasticity of OL lineage cells observed in the spinal cord following peripheral axon injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In Vivo Zonal Variation and Liver Cell-Type Specific NF-κB Localization after Chronic Adaptation to Ethanol and following Partial Hepatectomy.

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Harshavardhan Nilakantan

Full Text Available NF-κB is a major inflammatory response mediator in the liver, playing a key role in the pathogenesis of alcoholic liver injury. We investigated zonal as well as liver cell type-specific distribution of NF-κB activation across the liver acinus following adaptation to chronic ethanol intake and 70% partial hepatectomy (PHx. We employed immunofluorescence staining, digital image analysis and statistical distributional analysis to quantify subcellular localization of NF-κB in hepatocytes and hepatic stellate cells (HSCs. We detected significant spatial heterogeneity of NF-κB expression and cellular localization between cytoplasm and nucleus across liver tissue. Our main aims involved investigating the zonal bias in NF-κB localization and determining to what extent chronic ethanol intake affects this zonal bias with in hepatocytes at baseline and post-PHx. Hepatocytes in the periportal area showed higher NF-κB expression than in the pericentral region in the carbohydrate-fed controls, but not in the ethanol group. However, the distribution of NF-κB nuclear localization in hepatocytes was shifted towards higher levels in pericentral region than in periportal area, across all treatment conditions. Chronic ethanol intake shifted the NF-κB distribution towards higher nuclear fraction in hepatocytes as compared to the pair-fed control group. Ethanol also stimulated higher NF-κB expression in a subpopulation of HSCs. In the control group, PHx elicited a shift towards higher NF-κB nuclear fraction in hepatocytes. However, this distribution remained unchanged in the ethanol group post-PHx. HSCs showed a lower NF-κB expression following PHx in both ethanol and control groups. We conclude that adaptation to chronic ethanol intake attenuates the liver zonal variation in NF-κB expression and limits the PHx-induced NF-κB activation in hepatocytes, but does not alter the NF-κB expression changes in HSCs in response to PHx. Our findings provide new