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Sample records for exercise-induced n-terminal nt

  1. N-terminal prohormone brain natriuretic peptide (NT-proBNP as a noninvasive marker for restrictive syndromes

    Directory of Open Access Journals (Sweden)

    C. Mady

    2008-08-01

    Full Text Available Constrictive pericarditis (CP and restrictive cardiomyopathy share many similarities in both their clinical and hemodynamic characteristics and N-terminal prohormone brain natriuretic peptide (NT-proBNP is a sensitive marker of cardiac diastolic dysfunction. The objectives of the present study were to determine whether serum NT-proBNP was high in patients with endomyocardial fibrosis (EMF and CP, and to investigate how this relates to diastolic dysfunction. Thirty-three patients were divided into two groups: CP (16 patients and EMF (17 patients. The control group consisted of 30 healthy individuals. Patients were evaluated by bidimensional echocardiography, with restriction syndrome evaluated by pulsed Doppler of the mitral flow and serum NT-proBNP measured by immunoassay and detected by electrochemiluminescence. Spearman correlation coefficient was used to analyze the association between log NT-proBNP and echocardiographic parameters. Log NT-proBNP was significantly higher (P < 0.05 in CP patients (log mean: 2.67 pg/mL; 95%CI: 2.43-2.92 log pg/mL and in EMF patients (log mean: 2.91 pg/mL; 95%CI: 2.70-3.12 log pg/mL compared with the control group (log mean: 1.45; 95%CI: 1.32-1.60 log pg/mL. There were no statistical differences between EMF and CP patients (P = 0.689 in terms of NT-proBNP. The NT-proBNP log tended to correlate with peak velocity of the E wave (r = 0.439; P = 0.060, but not with A wave (r = -0.399; P = 0.112. Serum NT-proBNP concentration can be used as a marker to detect the presence of diastolic dysfunction in patients with restrictive syndrome; however, serum NT-proBNP levels cannot be used to differentiate restrictive cardiomyopathy from CP.

  2. Multicenter evaluation of plasma N-terminal probrain natriuretic peptide (NT-pro BNP) as a biochemical screening test for asymptomatic (occult) cardiomyopathy in cats.

    Science.gov (United States)

    Fox, P R; Rush, J E; Reynolds, C A; Defrancesco, T C; Keene, B W; Atkins, C E; Gordon, S G; Schober, K E; Bonagura, J D; Stepien, R L; Kellihan, H B; Macdonald, K A; Lehmkuhl, L B; Nguyenba, T P; Sydney Moise, N; Lefbom, B K; Hogan, D F; Oyama, M A

    2011-01-01

    B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved. Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters. One hundred and fourteen normal, healthy cats; 113 OCM cats. Prospective, multicenter, case-controlled study. NT-proBNP was prospectively measured and cardiac status was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis. NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P LVs (ρ = 0.33; P 46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L cut-off was 100% specific, 70.8% sensitive. Plasma NT-proBNP concentration reliably discriminated normal from OCM cats, and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and disease progression. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  3. 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

  4. N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE (NT-PROBNP) SERUM CONCENTRATIONS IN APPARENTLY HEALTHY BOSNIAN WOMEN

    OpenAIRE

    Hadžović-Džuvo, Almira; Kučukalić-Selimović, Elma; Nakaš-Ićindić, Emina; Zaćiragić, Asija; Dražeta, Zdenka

    2007-01-01

    Brain natriuretic peptide (BNP) is a cardiac hormone secreted predominantly from the ventricles. This hormone is produced as pre-prohormone BNP (pro BNP), than cleaved by corine to biologically active 32-aminoacid BNP and non-biologically active N-terminal-pro brain natriuretic peptide (NTproBNP). NTproBNP has been found to be a useful marker for the diagnosis of heart failure and left ventricular systolic dysfunction. Recent studies showed that concentration of BNP and NTproBNP predict cardi...

  5. N-terminal proB-type natriuretic peptide (NT-proBNP) concentrations in elite rugby players at rest and after active and passive recovery following strenuous training sessions.

    Science.gov (United States)

    Banfi, Giuseppe; D'Eril, Gianlodovico Melzi; Barassi, Alessandra; Lippi, Giuseppe

    2008-01-01

    The serum biomarker N-terminal proB-type natriuretic peptide (NT-proBNP), a cleaved fragment of the brain natriuretic peptide (BNP) precursor (amino acids 1-76), is accepted as a standard marker for evaluating and monitoring cardiac injury characterized by myocardial wall stress. Strenuous exercise may generate transitory ischemia, myocardial stress and diastolic left ventricular dysfunction, possibly inducing increased concentrations of NT-proBNP. A purported caveat to prolonged strenuous exercise is based on evidence for biochemical and structural signs of heart dysfunction in recreational athletes after continuous exertion. We compared NT-proBNP levels in three groups of physically fit subjects: top-level rugby players, professional soccer players and healthy controls. NT-proBNP concentrations were measured at rest and after an intensive training session followed by two different recovery strategies (passive or active). A comparison of the three samples showed that NT-proBNP concentrations in the rugby players were lower than those in controls at rest and were similar to those in professional soccer players. Elevated post-training NT-proBNP levels were unaffected by the type of recovery. The relatively high NT-proBNP levels after active recovery when psychophysical stress is higher, because of cycling and cold water immersion, suggest that not only endurance exercise, but also strenuous, stressful short exercise can induce an increase in NT-proBNP concentrations. In this sample of professional athletes, NT-proBNP was low at rest, and the increase after physical exercise was physiological.

  6. Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in dialysis patients.

    Science.gov (United States)

    Prado-Uribe, María Del Carmen; Ventura, María-de-Jesús; Ávila-Díaz, Marcela; Mora, Carmen J; Méndez-Durán, Antonio; Villanueva-Noches, Diana; Cisneros, Alejandra; Ilabaca, Begoña; Cueto-Manzano, Alfonso; García-Contreras, Fernando; Lindholm, Bengt; García-López, Elvia; Paniagua, Ramón

    Low thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. TH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. Low total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. Low total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  7. NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?).

    Science.gov (United States)

    Stienen, Susan; Salah, Khibar; Moons, Arno H; Bakx, Adrianus L; van Pol, Petra; Kortz, R A Mikael; Ferreira, João Pedro; Marques, Irene; Schroeder-Tanka, Jutta M; Keijer, Jan T; Bayés-Genis, Antoni; Tijssen, Jan G P; Pinto, Yigal M; Kok, Wouter E

    2018-04-17

    The concept of natriuretic peptide guidance has been extensively studied in patients with chronic heart failure (HF), with only limited success. The effect of NT-proBNP (N-terminal probrain natriuretic peptide)-guided therapy in patients with acute decompensated HF using a relative NT-proBNP target has not been investigated. This study aimed to assess whether NT-proBNP-guided therapy of patients with acute decompensated HF using a relative NT-proBNP target would lead to improved outcomes compared with conventional therapy. We conducted a prospective randomized controlled trial to study the impact of in-hospital guidance for acute decompensated HF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. Patients with acute decompensated HF with NT-proBNP levels >1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point was dual: a composite of all-cause mortality and HF readmissions in 180 days and the number of days alive out of the hospital in 180 days. Secondary end points were all-cause mortality within 180 days, HF readmissions within 180 days, and a composite of all-cause mortality and HF readmissions within 90 days. Significantly more patients in the NT-proBNP-guided therapy group were discharged with an NT-proBNP reduction of >30% (80% versus 64%, P =0.001). Nonetheless, NT-proBNP-guided therapy did not significantly improve the combined event rate for all-cause mortality and HF readmissions (hazard ratio, 0.96; 95% confidence interval, 0.72-1.37; P =0.99) or the median number of days alive outside of the hospital (178 versus 179 days for NT-proBNP versus conventional patients, P =0.39). Guided therapy also did not significantly improve any of the secondary end points. The PRIMA II trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure

  8. Exercise-Induced Bronchoconstriction

    Science.gov (United States)

    ... Conditions & Treatments ▸ Conditions Dictionary ▸ Exercise-Induced Bronchoconstriction Share | Exercise-Induced Bronchoconstriction (EIB) « Back to A to Z Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced ...

  9. Descenso de los niveles de propéptido natriurético de tipo B-N terminal luego de la reversión de pacientes con fibrilación auricular y función ventricular conservada NT-Pro-BNP levels performance before and after reversion to sinus rhythm in patients with preserved ventricular function

    Directory of Open Access Journals (Sweden)

    Claudio Higa

    2011-04-01

    Full Text Available El objetivo fue comparar los niveles de Pro Péptido Natriurético tipo B-N terminal (Pro-BNP-NT basales y post reversión en pacientes con fibrilación auricular solitaria (FAS de comienzo reciente y con función ventricular izquierda conservada. Se determinaron niveles del Pro BNP NT antes y después de su reversión en treinta pacientes con FAS de comienzo reciente y fracción de eyección de ventrículo izquierdo ≥ 50%. Basalmente, los niveles de Pro BNP NT fueron significativamente más elevados respecto a un grupo control sano: 529 pg/ml (157-1763 versus 31.5 pg/ml (24-76, p Our objective was to evaluate changes of N-terminal pro-BNP (NT-Pro-BNP levels at baseline and after restoration to sinus rhythm in hemodynamic stable patients with lone atrial fibrillation (LAF with preserved left ventricular function. NT-Pro-BNP levels were obtained before and after cardioversion in thirty hemodynamic stable patients with LAF and preserved left ventricular function. At baseline levels of NT-Pro BNP levels were significatively higher than a normal control group. NTPro-BNP levels decreased significantly following cardioversion from 529 (157-1763 to 318 (98-870 pg/ml, p < 0.0001. Decreasing of N-terminal pro-BNP concentrations was observed after any mode of cardioversion: electrical or pharmacologic, 345 (153-1151 pg/ml to 169 (86-407 pg/ml, p: 0.02 and from 1624 (541-4010 pg/ml to 856 (532-1160 pg/ml, p < 0.001, respectively. N-terminal pro-BNP decreasing was observed mainly in patients with length of LAF longer than 8 hours: 1289 (338-2103 to 410 (169-905 pg/ml, p < 0.001 but no difference was detected when such length was less than 8 hours: 274 (137-2300 to 286 (82-1440, p = NS. Our study showed that baseline levels of NT-pro-BNP decreased shortly after reversion of patients with LAF to sinus rhythm. This performance occurs predominantly in patients with LAF length of at least eight hours.

  10. The Association of Five-Year Changes in the Levels of N-Terminal Fragment of the Prohormone Brain-Type Natriuretic Peptide (NT-proBNP) with Subsequent Heart Failure and Death in Patients with Stable Coronary Artery Disease: The Heart and Soul Study.

    Science.gov (United States)

    Mishra, Rakesh K; Judson, Gregory; Christenson, Robert H; DeFilippi, Christopher; Wu, Alan H B; Whooley, Mary A

    The N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) is a powerful predictor of adverse outcomes in patients with coronary artery disease (CAD). However, little is known regarding the prognostic significance of longitudinal changes in NT-proBNP levels. We evaluated the ability of 5-year changes in NT-proBNP levels to predict subsequent heart failure (HF) hospitalization or cardiovascular (CV) death in 635 participants with stable CAD enrolled in the Heart and Soul Study. The median (IQR) 5-year change in NT-proBNP was 50 pg/mL (-5 to +222). During an average of 4.0 ± 1.4 years follow-up (i.e., 9 years from the baseline measurement), there were 67 events. Participants with 5-year changes in the highest quartile (≥ 223 pg/mL increase in NT-proBNP) had an almost 4-fold greater risk of subsequent HF or CV death than those in the lowest quartile of ≤-5 pg/mL (HR 3.8; 95% CI 2.0-7.3; p < 0.001). This association remained strong after adjustment for demographic variables, comorbidities, left ventricular mass index, systolic and diastolic function, and baseline and follow-up NT-proBNP levels (HR 3.9; 95% CI 1.1-13.4; p = 0.01). Changes in NT-proBNP levels at 5 years predict subsequent HF or CV death in patients with stable CAD, independent of other prognostic markers, including baseline and follow-up NT-proBNP levels. A stable NT-proBNP level predicts a low risk of subsequent events. © 2017 S. Karger AG, Basel.

  11. [Exercise induced hyponatremia].

    Science.gov (United States)

    Hadad, Eran; Rosen, Eli; Heled, Yuval; Moran, Daniel S; Schindel, Yair

    2004-05-01

    A normal water-electrolyte balance is essential for normal function of body systems during physical activity. During recent years, awareness of the importance of drinking amongst athletes and Israeli Defense Force (IDF) soldiers, in particular, has been highlighted. A large number of athletes tend to drink prior to, during and after their exercise in order to enhance physical abilities and to prevent heat casualties and dehydration. However, excessive water consumption combined with sweat induced electrolytes loss during physical activity, may cause hyponatremia in extreme cases. Recently, several cases of exercise induced hyponatremia were reported in the IDF, resulting from improper water consumption. In this article, we describe a clinical case of exercise-induced hyponatremia in a soldier and a review of the literature, including the etiology, clinical characterization and recommended treatment. Moreover, water consumption recommendations with regard to physical activity are presented. The application of such recommendations may prevent future events of exercise-induced hyponatremia.

  12. Exercise-induced rhabdomyolysis.

    Science.gov (United States)

    Lee, George

    2014-11-03

    Exercise-induced rhabdomyolysis, or exertional rhabdomyolysis (ER), is a clinical entity typically considered when someone presents with muscle stiffness, swelling, and pain out of proportion to the expected fatigue post exercise. The diagnosis is confirmed by myoglobinuria, and an elevated serum Creatinine Phosphokinase (CPK) level, usually 10 times the normal range. However, an elevation in CPK is seen in most forms of strenuous exercise, up to 20 times the upper normal range. Therefore, there is no definitive pathologic CPK cut-off. Fortunately the dreaded complication of acute renal failure is rare compared to other forms rhabdomyolysis. We review the risks, diagnosis, clinical course and treatment for exercise- induced rhabdomyolysis.

  13. Exercise-Induced Asthma

    Science.gov (United States)

    ... January 2014 More on this topic for: Parents Kids Teens Can Kids and Teens With Asthma Play Sports? Asthma Center When to Go to the ER if Your Child Has Asthma Kids and Exercise Asthma Triggers Word! Exercise-Induced Asthma ...

  14. Urinary N-Terminal Prohormone Brain Natriuretic Peptide Excretion in Patients With Chronic Heart Failure

    NARCIS (Netherlands)

    Linssen, Gerard C. M.; Damman, Kevin; Hillege, Hans L.; Navis, Gerjan; van Veldhuisen, Dirk J.; Voors, Adriaan A.

    2009-01-01

    Background-Urinary excretion is currently regarded as the main mechanism of elimination of N-terminal prohormone brain natriuretic peptide (NT-proBNP). The clinical implications and the value of measurement of urinary NT-proBNP in patients with heart failure are largely unknown. Methods and

  15. Exercise-Induced Bronchoconstriction (EIB)

    Science.gov (United States)

    ... Listing Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced asthma, is a narrowing of the airways causing difficulty ... exercise. Yet some people who don’t have asthma experience symptoms only when they exercise. Symptoms include: • Shortness of breath • Coughing • Wheezing • Tight ...

  16. Exercise-Induced Bronchoconstriction Quiz

    Science.gov (United States)

    ... and ask for appropriate care. Question 2 My child with asthma or exercise-induced bronchoconstriction can't exercise and ... to respond to problems. Question 5 If my child has asthma, he or she can never be an Olympic ...

  17. N-terminal Pro-B-type natriuretic peptide: a measure of significant patent cuctus arteriosus

    LENUS (Irish Health Repository)

    OFarombi-Oghuvbu, IO

    2008-01-24

    Background: B type natriuretic peptide (BNP) is a marker for ventricular dysfunction secreted as a pre-prohormone, Pro-B-type natriuretic peptide (ProBNP), and cleaved into BNP and a biologically inactive fragment, N-terminal pro-B-type natriuretic peptide (NT-proBNP). Little is known about the clinical usefulness of NT-proBNP in preterm infants.\\r\

  18. Adolescents and Exercise Induced Asthma

    Science.gov (United States)

    Hansen, Pamela; Bickanse, Shanna; Bogenreif, Mike; VanSickle, Kyle

    2008-01-01

    This article defines asthma and exercise induced asthma, and provides information on the triggers, signs, and symptoms of an attack. It also gives treatments for these conditions, along with prevention guidelines on how to handle an attack in the classroom or on the practice field. (Contains 2 tables and 1 figure.)

  19. 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 ...

  20. Exercise-induced bronchospasm in children.

    Science.gov (United States)

    Randolph, Chris

    2008-04-01

    This review will encompass definition, history, epidemiology, pathogenesis, diagnosis, and management of exercise -induced bronchospasm in the pediatric individual with and without known asthma. Exercise induced asthma is the conventional term for transient airway narrowing in a known asthma in association with strenuous exercise usually lasting 5-10 minutes with a decline in pulmonary function by at least 10%. Exercise induced asthma will be referred to as exercise induced bronchospasm in an asthmatic. Exercise-induced bronchospasm (EIB ) is the same phenomenon in an individual without known asthma. EIB can be seen in healthy individuals including children as well as defense recruits and competitive or elite athletes. The diagnosis with objective exercise challenge methods in conjunction with history is delineated. Management is characterized with pharmacotherapy and non pharmacotherapeutic measures for underlying asthma as well as exercise induced bronchospasm and inhalant allergy. Children can successfully participate in all sports if asthma is properly managed.

  1. Exercise-induced cardiac remodeling.

    Science.gov (United States)

    Weiner, Rory B; Baggish, Aaron L

    2012-01-01

    Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Towards the N-terminal acetylome

    DEFF Research Database (Denmark)

    Zhang, Xumin; Højrup, Peter

    2013-01-01

    Protein N-terminal acetylation (N(α)-acetylation) is observed widely from prokaryotes to eukaryotes. It gains increased importance in biological field, due to its multiple roles in many aspects of the protein life, such as assembly, stability, activity, and location. Today, mass spectrometry (MS...

  3. N-terminal pro-B-type natriuretic peptide for the prognostic prediction of severe enterovirus 71-associated hand, foot, and mouth disease

    OpenAIRE

    Jun Qiu; Xiulan Lu; Pingping Liu; Xinping Zhang; Chao Zuo; Zhenghui Xiao

    2017-01-01

    Objective: The aim of this study was to determine whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) can predict impending brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, cardiopulmonary failure, and death in children with severe enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD). Methods: Plasma NT-proBNP levels of 282 children with severe EV71-associated HFMD were measured. Results: NT-proBNP levels were significantly higher in patients wit...

  4. Research progress of exercise-induced fatigue

    Directory of Open Access Journals (Sweden)

    Peng-yi DAI

    2016-12-01

    Full Text Available Exercise-induced fatigue is a comprehensive response to a variety of physiological and biochemical changes in the body, and can affect people's quality of life to different extents. If no timely recovery after occurrence of fatigue, accumulated gradually, it can lead to "burnout", a "overtraining syndrome", "chronic fatigue syndrome", etc., which will cause endocrine disturbance, immune suppression, even physical illness. Exercise-induced fatigue becomes an important factor endangering human health. In recent years, many experts and scholars at home and abroad are committed to the research of exercise-induced fatigue, and have put forward a variety of hypothesis to explain the cause of exercise-induced fatigue. They expect to find out the methods for preventing and eliminating exercise-induced fatigue. This article discusses mainly the pathogenesis, model building, elimination/ relief, etc. of exercise-induced fatigue to point out the research achievements of exercise-induced fatigue and its existing problems. DOI: 10.11855/j.issn.0577-7402.2016.11.14

  5. Carbamylation of N-terminal proline.

    Science.gov (United States)

    Olajuyigbe, Folasade M; Demitri, Nicola; Ajele, Joshua O; Maurizio, Elisa; Randaccio, Lucio; Geremia, Silvano

    2010-09-09

    Protein carbamylation is of great concern both in vivo and in vitro. Here, we report the first structural characterization of a protein carbamylated at the N-terminal proline. The unexpected carbamylation of the α-amino group of the least reactive codified amino acid has been detected in high-resolution electron density maps of a new crystal form of the HIV-1 protease/saquinavir complex. The carbamyl group is found coplanar to the proline ring with a trans conformation. The reaction of N-terminal with cyanate ion derived from the chaotropic agent urea was confirmed by mass spectra analysis on protease single crystals. Implications of carbamylation process in vitro and in vivo are discussed.

  6. Elevated plasma N-terminal ProBNP levels in unmedicated patients with major depressive disorder.

    Science.gov (United States)

    Politi, Pierluigi; Minoretti, Piercarlo; Piaggi, Noemi; Brondino, Natascia; Emanuele, Enzo

    2007-05-07

    There is considerable evidence that cardiovascular diseases are more prevalent in patients with major depressive disorder (MDD). Secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) increases in several cardiac illnesses, making this neurohormone a reliable diagnostic and prognostic biomarker of cardiovascular risk. We measured plasma NT-proBNP levels in the following three groups of subjects free of overt cardiovascular disease: unmedicated patients with MDD (n=40), unmedicated patients with schizophrenia (n=44), and normal control subjects (n=42). The severity of depressive symptoms was rated using the Hamilton Depression Rating Scale (HAMD). Plasma NT-proBNP levels were assayed by ELISA. Plasma NT-proBNP levels were significantly higher in the MDD group (median: 217.1 pmol/L; interquartile range: 179.4-277.1 pmol/L) than in patients with schizophrenia (175.7 pmol/L [139.0-218.9]; P<0.05) or in the control group (158.9 pmol/L [98.3-212.1]; P<0.001). Among patients with MDD, there was a significant positive correlation (Spearman's rank correlation=0.422, P=0.008) between plasma NT-proBNP and HAMD scores. Altogether, our results indicate that elevated NT-proBNP levels may play a role in linking MDD with increased cardiovascular risk.

  7. N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage.

    Directory of Open Access Journals (Sweden)

    Hee-Jung Kim

    Full Text Available Ubiquitin C-terminal hydrolase-L1 (UCH-L1 has been proposed as one of the Parkinson's disease (PD related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen-deuterium exchange (HDX with tandem mass spectrometry (MS studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD.

  8. 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

  9. 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...... patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status. CLINICAL TRIAL REGISTRATION: URL: https...

  10. [Exercise-induced rhabdomyolysis - a new trend?

    Science.gov (United States)

    Fardal, Hilde; Gøransson, Lasse G

    2016-10-01

    The purpose of this study was to investigate whether or not there has been an increase in the number of admissions for exercise-induced rhabdomyolysis at Stavanger University Hospital (SUS) in recent years. The study is a retrospective review of patients discharged over the period January 2010 to March 2015 with a diagnosis of exercise-induced rhabdomyolysis and with maximum creatine kinase (CK) levels more than ten times the upper reference limit. A total of 33 patients, 21 women and 12 men, with a median age of 28 years (18 - 68), were included in the study. Of the 33 patients, three quarters (25) were admitted in 2014 - 15, compared with eight over the period 2010 - 13. One patient developed kidney failure that required dialysis. The treatment depended more on the attending physician and department than on the patient's clinical condition and CK-level, but this did not seem to affect the rate of complications. The incidence of exercise-induced rhabdomyolysis at SUS increased from autumn 2014, and this coincided with increased media attention and a new exercise trend. We recommend standardising the treatment of exercise-induced rhabdomyolysis, as current treatment recommendations are based on rhabdomyolysis triggered by causes other than exercise.

  11. Exercise-induced rhabdomyolysis - a patient series.

    Science.gov (United States)

    Tazmini, Kiarash; Schreiner, Christoffer; Bruserud, Sidsel; Raastad, Truls; Solberg, Erik Ekker

    2017-11-14

    No guidelines are available for the treatment and follow up of exercise-induced rhabdomyolysis. The purpose of this study was to describe the treatment, complications and follow-up of patients with exercise-induced rhabdomyolysis at Diakonhjemmet Hospital. A retrospective observational study from 2011 up to and including 2015 of patients with exercise-induced rhabdomyolysis ≥ 18 years and with creatine kinase > 5 000 IU/l. We registered a total of 42 patients and obtained informed consent from 31. Twenty were treated as inpatients with a median hospitalisation time of 2.5 (1–6) days. Median creatine kinase was 36 797 (17 172–53 548) IU/l upon admission and 16 051 (11 845–26 505) IU/l at discharge. Median intravenous fluid volume was 6 000 (1 000–27 700) ml. Eleven patients underwent urinary alkalinisation. None developed severe kidney injury or other serious complications such as electrolyte imbalance, compartment syndrome or disseminated intravascular coagulation, either during hospitalisation or in the course of the study period. Healthy persons with exercise-induced rhabdomyolysis have a very low risk of complications. Our patients are treated as outpatients or considered for discharge with creatine kinase < 40 000 IU/l measured at least three days after their workout, and if they have no risk factors or other complications.

  12. Plasma NT-proBNP and White Matter Hyperintensities in Type 2 Diabetic Patients

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Garde, Ellen; Skimminge, Arnold

    2012-01-01

    Elevated plasma N-terminal (NT)-proBNP from the heart as well as white matter hyperintensities (WMH) in the brain predict cardiovascular (CV) mortality in the general population. The cause of poor prognosis associated with elevated P-NT-proBNP is not known but WMH precede strokes in high risk pop...... populations. We assessed the association between P-NT-proBNP and WMH or brain atrophy measured with magnetic resonance imaging (MRI) in type 2 diabetic patients, and age-matched controls.......Elevated plasma N-terminal (NT)-proBNP from the heart as well as white matter hyperintensities (WMH) in the brain predict cardiovascular (CV) mortality in the general population. The cause of poor prognosis associated with elevated P-NT-proBNP is not known but WMH precede strokes in high risk...

  13. High circulating N-terminal pro-B-type natriuretic peptide is associated with greater systolic cardiac dysfunction and nonresponsiveness to fluids in septic vs nonseptic critically ill patients

    NARCIS (Netherlands)

    Hartemink, K.J.; Twisk, J.W.; Groeneveld, A.B.J.

    2011-01-01

    Purpose: It is still unclear whether circulating levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) reflect cardiac filling and function in the critically ill patient, particularly during sepsis and a proinflammatory response that may induce NT-proBNP release from the heart. Materials

  14. Serum levels of N-terminal proB-type natriuretic peptide in mechanically ventilated critically ill patients--relation to tidal volume size and development of acute respiratory distress syndrome

    NARCIS (Netherlands)

    Determann, Rogier M.; Royakkers, Annick A. N. M.; Schaefers, Jacqueline; de Boer, Anita M.; Binnekade, Jan M.; van Straalen, Jan P.; Schultz, Marcus J.

    2013-01-01

    Serum levels of N-terminal proB-type natriuretic peptide (NT-proBNP) are elevated in patients acute respiratory distress syndrome (ARDS). Recent studies showed a lower incidence of acute cor pulmonale in ARDS patients ventilated with lower tidal volumes. Consequently, serum levels of NT-proBNP may

  15. N-terminal pro-brain natriuretic peptide levels associated with severe hand, foot and mouth disease

    OpenAIRE

    Deng, Hui-Ling; Zhang, Yu-Feng; Li, Ya-Ping; Zhang, Yu; Xie, Yan; Wang, Jun; Wang, Xiao-Yan; Dang, Shuang-Suo

    2016-01-01

    Background Severe hand, foot, and mouth disease (HFMD) is sometimes associated with serious complications such as acute heart failure that can cause substantial child mortality. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive and specific biomarker of congestive heart failure. The aim of this study was to use plasma NT-proBNP levels to establish the severity of childhood HFMD. Methods A retrospective study was performed in 128 Chinese patients with severe HFMD and 88 patie...

  16. Crystal Structure of the N-terminal Domain of the Group B Streptococcus Alpha C Protein

    Energy Technology Data Exchange (ETDEWEB)

    Auperin,T.; Bolduc, G.; Baron, M.; Heroux, A.; Filman, D.; Madoff, L.; Hogle, J.

    2005-01-01

    Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis among neonates and an important cause of morbidity among pregnant women and immunocompromised adults. Invasive diseases due to GBS are attributed to the ability of the pathogen to translocate across human epithelial surfaces. The alpha C protein (ACP) has been identified as an invasin that plays a role in internalization and translocation of GBS across epithelial cells. The soluble N-terminal domain of ACP (NtACP) blocks the internalization of GBS. We determined the 1.86-{angstrom} resolution crystal structure of NtACP comprising residues Ser{sup 52} through Leu{sup 225} of the full-length ACP. NtACP has two domains, an N-terminal {beta}-sandwich and a C-terminal three-helix bundle. Structural and topological alignments reveal that the {beta}-sandwich shares structural elements with the type III fibronectin fold (FnIII), but includes structural elaborations that make it unique. We have identified a potential integrin-binding motif consisting of Lys-Thr-Asp{sup 146}, Arg{sup 110}, and Asp{sup 118}. A similar arrangement of charged residues has been described in other invasins. ACP shows a heparin binding activity that requires NtACP. We propose a possible heparin-binding site, including one surface of the three-helix bundle, and nearby portions of the sandwich and repeat domains. We have validated this prediction using assays of the heparin binding and cell-adhesion properties of engineered fragments of ACP. This is the first crystal structure of a member of the highly conserved Gram-positive surface alpha-like protein family, and it will enable the internalization mechanism of GBS to be dissected at the atomic level.

  17. N-terminal-pro-brain natriuretic peptide elevations in the course of septic and non-septic shock reflect systolic left ventricular dysfunction assessed by transpulmonary thermodilution

    NARCIS (Netherlands)

    A.J. Groeneveld; R.J. Trof (R.)

    2016-01-01

    textabstractBackground: The cardiac correlates, if any, of N-terminal probrain natriuretic peptide (NT-proBNP) levels in septic and non-septic shock patients remain controversial. Methods: In the 38 septic and 22 non-septic shock patients in the transpulmonary thermodilution arm of a previous

  18. Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex

    DEFF Research Database (Denmark)

    Olsen, M.H.; Hansen, T.W.; Christensen, M.K.

    2008-01-01

    BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated...

  19. The relationship between N-terminal pro-brain natriuretic peptide and risk for hospitalization and mortality is curvilinear in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Corell, Pernille

    2007-01-01

    BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore, a clinica......BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) carries prognostic information in patients with chronic heart failure and predicts risk for mortality and cardiovascular events. It is unknown whether NT-proBNP predicts risk for hospitalization for any cause. Furthermore....... METHODS: Data from 345 patients with chronic heart failure were collected prospectively in our heart failure clinic, and the patients were followed for 28 months (median). Seventy patients died, and 201 patients were hospitalized. Cox proportional hazard models for mortality and hospitalization were...... constructed with NT-proBNP as a dichotomous (median 1381 pg/mL) and a continuous variable (log2 NT-proBNP). RESULTS: Patients with supramedian levels of NT-proBNP had a 2.40-fold (95% CI 1.40-4.10) increased risk for mortality and 1.71-fold (95% CI 1.24-2.36) increased risk for hospitalization. The effect...

  20. N-terminal pro-atrial natriuretic peptide response to acute exercise in depressed patients and healthy controls

    DEFF Research Database (Denmark)

    Krogh, Jesper; Ströhle, Andreas; Westrin, Asa

    2011-01-01

    BACKGROUND: The dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in major depression includes hyperactivity and reduced feedback inhibition. Atrial natriuretic peptide (ANP) is able to reduce the HPA-axis response to stress and has an anxiolytic effect in rodents and humans. We hypothesized...... that patients with depression would have an attenuated N-terminal proANP (NT-proANP) response to acute exercise compared to healthy controls. Secondly, we aimed to assess the effect of antidepressants on NT-proANP response to acute exercise. METHODS: We examined 132 outpatients with mild to moderate depression...... (ICD-10) and 44 healthy controls, group matched for age, sex, and BMI. We used an incremental bicycle ergometer test as a physical stressor. Blood samples were drawn at rest, at exhaustion, and 15, 30, and 60min post-exercise. RESULTS: The NT-proANP response to physical exercise differed between...

  1. Biologic variability of N-terminal pro-brain natriuretic peptide in adult healthy cats.

    Science.gov (United States)

    Harris, Autumn N; Estrada, Amara H; Gallagher, Alexander E; Winter, Brandy; Lamb, Kenneth E; Bohannon, Mary; Hanscom, Jancy; Mainville, Celine A

    2017-02-01

    Objectives The biologic variability of N-terminal pro-brain natriuretic peptide (NT-proBNP) and its impact on diagnostic utility is unknown in healthy cats and those with cardiac disease. The purpose of this study was to determine the biologic variation of NT-proBNP within-day and week-to-week in healthy adult cats. Methods Adult cats were prospectively evaluated by complete blood count (CBC), biochemistry, total thyroxine, echocardiography, electrocardiography and blood pressure, to exclude underlying systemic or cardiac disease. Adult healthy cats were enrolled and blood samples were obtained at 11 time points over a 6 week period (0, 2 h, 4 h, 6 h, 8 h, 10 h and at weeks 2, 3, 4, 5 and 6). The intra-individual (coefficient of variation [CV I ]) biologic variation along with index of individuality and reference change values (RCVs) were calculated. Univariate models were analyzed and included comparison of the six different time points for both daily and weekly samples. This was followed by a Tukey's post-hoc adjustment, with a P value of <0.05 being significant. Results The median daily and weekly CV I for the population were 13.1% (range 0-28.7%) and 21.2% (range 3.9-68.1%), respectively. The index of individuality was 0.99 and 1 for daily and weekly samples, respectively. The median daily and weekly RCVs for the population were 39.8% (range 17.0-80.5%) and 60.5% (range 20.1-187.8%), respectively. Conclusions and relevance This study demonstrates high individual variability for NT-proBNP concentrations in a population of adult healthy cats. Further research is warranted to evaluate NT-proBNP variability, particularly how serial measurements of NT-proBNP may be used in the diagnosis and management of cats with cardiac disease.

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

    Science.gov (United States)

    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

  3. 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

  4. N-terminal pro-B-type natriuretic peptide for the prognostic prediction of severe enterovirus 71-associated hand, foot, and mouth disease.

    Science.gov (United States)

    Qiu, Jun; Lu, Xiulan; Liu, Pingping; Zhang, Xinping; Zuo, Chao; Xiao, Zhenghui

    2017-01-01

    The aim of this study was to determine whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) can predict impending brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, cardiopulmonary failure, and death in children with severe enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD). Plasma NT-proBNP levels of 282 children with severe EV71-associated HFMD were measured. NT-proBNP levels were significantly higher in patients with elevated blood glucose (>7.8 mmol/l) and increased white blood cell counts (>14×10 9 /l). HFMD patients who had no complications had significantly lower NT-proBNP values than patients who died or had complications (pdisease in the intensive care unit. Serum NT-proBNP values ≥1300pg/ml on admission could be indicative of circulatory failure and increased mortality. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. 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]; Pmax]: 103.5-137.2%; range of absolute increase [min-max]: 23.5-304.0 ng/L). NT-proBNP concentrations decreased below the baseline value 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.

  6. A Clinical Study of the N-Terminal pro-Brain Natriuretic Peptide in Myocardial Injury after Neonatal Asphyxia.

    Science.gov (United States)

    Zhu, Rui; Nie, Zhenhong

    2016-04-01

    We aimed to study the changes of serum N-terminal pro-brain natriuretic to peptide (NT-proBNP) levels after asphyxia-induced myocardial injury in children and explore the relationship between serum NT-proBNP levels and neonatal asphyxia. One hundred and six cases of neonatal asphyxia were randomly selected for the study, including 46 severe cases with myocardial injury and 60 mild cases with no cardiac injury. Sixty-three healthy newborns were selected as the control group. The serum NT-proBNP level was detected using electrochemiluminescence. Creatine kinase MB (CK-MB) and serum sodium and calcium were measured simultaneously. The serum NT-proBNP level in the myocardial injury group was significantly higher than that of the noncardiac injury and control groups (p Asphyxia serum NT-proBNP and cardiac enzymes were significantly correlated. The median value of neonatal NT-proBNP was 1491 pg/mL at postnatal Day 3 (P3) and 1077 pg/mL at postnatal Day 14 (P14). The cutoff value for children with myocardial injury was 3612.5 pg/mL; the area under the receiver operating characteristic curve was 0.80 (p neonates with asphyxia and can guide its diagnosis. Copyright © 2016. Published by Elsevier B.V.

  7. Exercise-induced vocal cord dysfunction and exercise-induced laryngomalacia in children and adolescents: the same clinical syndrome?

    Science.gov (United States)

    Tilles, Stephen A; Ayars, Andrew G; Picciano, Joseph F; Altman, Kathrine

    2013-11-01

    Exercise-induced respiratory symptoms associated with paradoxical laryngeal motion are relatively common and often mistaken for asthma. Exercise-induced vocal cord dysfunction (VCD) and exercise-induced laryngomalacia (LM) have been described separately in the literature but have never been systematically compared. To compare subjects with a confirmed diagnosis of exercise-induced VCD or exercise-induced LM by performing a retrospective chart review of subjects who had symptoms provoked by a free running exercise challenge and documented concurrent paradoxical laryngeal motion. Demographic and clinical characteristics were analyzed in patients with confirmed paradoxical motion of the vocal cords (VCD) and those with paradoxical arytenoid motion without abnormal vocal cord movement (LM) during symptoms. Sixty subjects with exercise-induced LM and 83 subjects with exercise-induced VCD were identified. Subjects with confirmed exercise-induced VCD were slightly older, had a higher body mass index, and higher grade point averages compared with subjects with exercise-induced LM without abnormal vocal cord movement. There were no differences in sex distribution, presenting symptoms, reported aggravating factors other than exercise, atopic status, confirmed bronchospasm during symptoms, mean number of asthma controller medications at time of evaluation, level of athletic competition, reported history of acid reflux, reported history of psychiatric disorders, baseline lung function, or lung function during symptoms. Most subjects were not "elite" athletes and did not have a history of anxiety or depression. There were remarkably few differences between subjects with exercise-induced VCD and those with exercise-induced LM. Prospective controlled studies are needed to determine whether exercise-induced VCD and exercise-induced LM are in fact distinct syndromes. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. NT-proBNP

    DEFF Research Database (Denmark)

    Andersen, Charlotte; Mellemkjær, Søren; Hilberg, Ole

    2016-01-01

    BACKGROUND: Pulmonary hypertension (PH) is a serious complication to interstitial lung disease (ILD) and has a poor prognosis. PH is often diagnosed by screening with echocardiography followed by right heart catheterisation. A previous study has shown that a value of NT-pro-brain natriuretic...

  9. NT-proBNP, echocardiographic abnormalities and subclinical coronary artery disease in high risk type 2 diabetic patients

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Hansen, Peter R; Wiinberg, Niels

    2012-01-01

    Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P-NT-proBNP and the put......Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P......-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients...

  10. N-terminal pro-brain natriuretic peptide levels associated with severe hand, foot and mouth disease.

    Science.gov (United States)

    Deng, Hui-Ling; Zhang, Yu-Feng; Li, Ya-Ping; Zhang, Yu; Xie, Yan; Wang, Jun; Wang, Xiao-Yan; Dang, Shuang-Suo

    2016-10-19

    Severe hand, foot, and mouth disease (HFMD) is sometimes associated with serious complications such as acute heart failure that can cause substantial child mortality. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive and specific biomarker of congestive heart failure. The aim of this study was to use plasma NT-proBNP levels to establish the severity of childhood HFMD. A retrospective study was performed in 128 Chinese patients with severe HFMD and 88 patients with mild HFMD treated between January 2014 and October 2015. Univariate and multiple logistic regression analyses were used to analyze the risk factors for severe HFMD. NT-proBNP levels were analyzed in 128 severe HFMD patients, and the predictive value of NT-proBNP was assessed by receiver operating characteristic analyses. Multivariate analysis controlling for several potential confounders showed that enterovirus 71 infection [odds ratio (OR) 19.944, 95 % confidence interval (CI) 6.492-61.271], peripheral WBC count (OR 3.428, 95 % CI 1.186-9.914), fasting glucose (OR 19.428, 95 % CI 2.236-168.784), procalcitonin (OR 9.084, 95 % CI 3.462-23.837, and NT-proBNP (>125 pg/mL) (OR 16.649, 95 % CI 4.731-58.585) were each associated with the severity of HFMD. The 45 dead severe patients had higher pre-procedural levels of NT-proBNP than the 83 cured severe patients (12776 ± 13115 versus 1435 ± 4201 pg/mL, P < 0.001). An NT-proBNP cutoff value of 982 pg/mL predicted mortality with 87 % sensitivity and 86 % specificity. Plasma NT-pro-BNP level appears to be a useful biological marker for predicting the severity and mortality of HFMD.

  11. N-terminal pro-brain natriuretic peptide and renal insufficiency as predictors of mortality in pulmonary hypertension.

    Science.gov (United States)

    Leuchte, Hanno H; El Nounou, Michal; Tuerpe, Juergen Christian; Hartmann, Bertram; Baumgartner, Rainer A; Vogeser, Michael; Muehling, Olaf; Behr, Jürgen

    2007-02-01

    N-terminal pro-brain natriuretic peptide (NT-proBNP) is a byproduct of the brain natriuretic peptide (BNP) that was shown to be of prognostic value in pulmonary hypertension (PH). The role of NT-proBNP in PH has to be determined, especially under the influence of renal impairment that might lead to an accumulation of the peptide, and may be a sign of increased mortality per se. We assessed NT-proBNP, BNP, renal function, and hemodynamic parameters (during right-heart catheterization) in 118 consecutive patients with isolated PH, excluding left-heart disease. Depending on the calculated creatinine clearance, patients were classified into different groups of renal function. Correlation analysis was performed on all key parameters. Results were then compared between the levels of renal function. The prognostic value of each parameter was assessed during a mean follow-up period of 10 months. Twenty-two patients (approximately 19%) had significantly impaired renal function (creatinine clearance < 60 mL/min). Although the overall levels of NT-proBNP were correlated with hemodynamics, we observed no correlation in the group with significant renal dysfunction. Moreover, NT-proBNP was related to creatinine clearance. Finally, NT-proBNP and renal insufficiency were independent predictors of death during univariate and multivariate analysis, whereas BNP only predicted mortality in univariate analysis. The diagnostic accuracy of NT-proBNP as a parameter of the hemodynamic status is diminished by renal function. However, NT-proBNP could be superior to BNP as a survival parameter in PH because it integrates hemodynamic impairment and renal insufficiency, which serves as a sign of increased mortality per se.

  12. 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....

  13. Association between resting heart rate and N-terminal pro-brain natriuretic peptide in a community-based population study in Beijing

    Directory of Open Access Journals (Sweden)

    Cao R

    2014-12-01

    Full Text Available Ruihua Cao, Yongyi Bai, Ruyi Xu, Ping Ye Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, People’s Republic of China Background: N-terminal pro-brain natriuretic peptide (NT-proBNP is associated with an increased risk of cardiac insufficiency, which possibly leads to heart failure. However, the relationship between resting heart rate and NT-proBNP is unclear.Objective: This study focuses on this relativity between resting heart rate and plasma NT-proBNP levels in a surveyed community-based population.Methods: We evaluated the relativity between resting heart rate and plasma levels of NT-proBNP in 1,567 participants (mean age 61.0 years, range 21–96 years from a community-based population in Beijing, People’s Republic of China.Results: In patients with high resting heart rate (≥75 beats/min, NT-proBNP was higher than in those having low resting heart rate (<75 beats/min. In multiple linear stepwise regression analysis, plasma NT-proBNP was associated with resting heart rate (partial correlation coefficient, 0.82; 95% confidence interval, 0.18–1.51; P=0.011. A subsequent subgroup analysis revealed that the association between resting heart rate and plasma NT-proBNP was strengthened in subjects over 60 years old (partial correlation coefficient 1.28; 95% confidence interval, 0.49–2.36; P=0.031; while the relativity between resting heart rate and plasma NT-proBNP was not emerged in the younger subgroup (<60 years old.Conclusions: Resting heart rate was associated with plasma NT-proBNP in the elderly, which indicated a relationship between resting heart rate and cardiac function damage. Keywords: resting heart rate, N-terminal pro-brain natriuretic peptide, epidemiology, cardiac function, relationship

  14. NT-proBNP and exercise capacity in adult patients with congenital heart disease and a prosthetic valve : a multicentre PROSTAVA study

    NARCIS (Netherlands)

    Schoonbeek, R C; Pieper, P. G.; van Slooten, Y. J.; Freling, Hendrik G.; Sieswerda, G. T.; van Dijk, A. P. J.; Jongbloed, M. R. M.; Post, M. C.; Bouma, B. J.; Berger, R. M. F.; Ebels, T.; van Melle, J. P.

    2016-01-01

    Objectives N-terminal B-type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients

  15. NT-proBNP and exercise capacity in adult patients with congenital heart disease and a prosthetic valve: a multicentre PROSTAVA study

    NARCIS (Netherlands)

    Schoonbeek, R. C.; Pieper, P. G.; van Slooten, Y. J.; Freling, H. G.; Sieswerda, G. T.; van Dijk, A. P. J.; Jongbloed, M. R. M.; Post, M. C.; Bouma, B. J.; Berger, R. M. F.; Ebels, T.; van Melle, J. P.

    2016-01-01

    N-terminal B‑type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a

  16. Nuclear waste for NT

    International Nuclear Information System (INIS)

    Nelson, Brendan

    2005-01-01

    The Northern Territory may be powerless to block the dumping of low-level nuclear waste in the Territory under legislation introduced into Parliament by Minister for Education Science and Training, Dr Brendan Nelson, in October. Despite strong opposition to the dumping of nuclear waste in the NT, the Australian Government will be able to send waste to one of the three nominated Commonwealth-owned Defence sites within the NT under the Commonwealth Radioactive Waste Management Bill 2005 and the Commonwealth Radioactive Waste Management (Related Amendment) Bill 2005. The Bills veto recently drafted NT legislation designed to scuttle the plans. Low-level nuclear waste is stored at more than 100 sites around Australia, including hospitals, factories, universities and defence facilities. Medical isotopes produced at Lucas Heights and provided for medical procedures are the source of much of this waste, including some 16 cubic metres currently held at Darwin Hospital. Dr Nelson stressed that the Government would take all die necessary steps to comply with safety and regulatory precautions, including handling waste in line with relevant environmental, nuclear safety and proliferation safeguards

  17. The role of n terminal - probrain natriuretic peptide in the diagnosis of hemodynamic persistent asrteriosus ductus in premature neonates patient

    Science.gov (United States)

    Dasraf, D.; Djer, M. M.; Advani, N.

    2017-08-01

    Persistent ductus arteriosus is one of the most frequent congenital heart diseases found in infants, mainly in preterms. Echocardiography is the gold standard for the diagnosis of hemodynamically significant patent ductus arteriosus (hs-PDA) in preterm neonates. A few studies have suggested that the use of a simple blood assay to detect N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful in determining the diagnosis and management of hs-PDA. No such studies have been conducted in Indonesia, although the assay kit and characteristics of the patient (gestational age and chronological age) influence the accuracy of NT-proBNP levels in determining hs-PDA. The aim of this study was to determine the association between the NT-proBNP level and the prevalence of hs-PDA in an Indonesian patient population. A cross-sectional study was conducted at Dr. Cipto Mangunkusumo Hospital. PDA was determined using echocardiography in 49 preterm neonates (gestational age groups: non-PDA, non-hsPDA, and hs-PDA. The blood NT-proBNP level was then determined in the non-hsPDA and hs-PDA groups, and between-group differences were compared. Among the 49 neonates, 33 patients had PDA, and 16 of these had hs-PDA. The results revealed a significant association between the NT-proBNP level and hs-PDA (p < 0.001).

  18. N-terminal pro-brain natriuretic peptide and abnormal brain aging: The AGES-Reykjavik Study.

    Science.gov (United States)

    Sabayan, Behnam; van Buchem, Mark A; de Craen, Anton J M; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

    2015-09-01

    To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. © 2015 American Academy of Neurology.

  19. Blood N-terminal Pro-brain Natriuretic Peptide and Interleukin-17 for Distinguishing Incomplete Kawasaki Disease from Infectious Diseases.

    Science.gov (United States)

    Wu, Ling; Chen, Yuanling; Zhong, Shiling; Li, Yunyan; Dai, Xiahua; Di, Yazhen

    2015-06-01

    To explore the diagnostic value of blood N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin-17(IL-17) for incomplete Kawasaki disease. Patients with Kawasaki disease, Incomplete Kawasaki disease and unclear infectious fever were included in this retrospective study. Their clinical features, and laboratory test results of blood NT-proBNP and IL-17 were collected and compared. 766 patients with complete clinical information were recruited, consisting of 291 cases of Kawasaki disease, 74 cases of incomplete Kawasaki disease, and 401 cases of unclear infectious diseases. When the consistency with indicator 2 and 3 in Kawasaki disease diagnosis criteria was assessed with blood IL-17 ?11.55 pg/mL and blood NT-proBNP ? 225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases reached 86.5% and 94.8%, respectively. When we chose the consistency with indicator 1 and 2 in Kawasaki disease diagnosis criteria, the appearance of decrustation and/or the BCG erythema, blood IL-17 ?11.55 pg/mL and blood NT-Pro BNP ?225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases was 43.2% and 100%, respectively. Blood NT-proBNP and IL-17 are useful laboratory indicators for distinguishing incomplete Kawasaki disease and infectious diseases at the early stage.

  20. Analysis of N-terminal pro-brain natriuretic peptide levels in patients with chronic heart failure

    International Nuclear Information System (INIS)

    Fu Xiao; Zhang Xingping; Zhou Kejian

    2011-01-01

    To investigate the changes and its clinical significance of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with chronic heart failure(CHF), 128 patients with decompensated CHF and 20 patients without structural heart disease were selected as CHF and control group. All subjects were evaluated heart function by New York Heart Association (NYHA) class. The serum NT-proBNP levels were assayed by electrochemiluminescence double antibody sandwich immunoassay. Left ventricular ejection fraction (LVEF) was detected by color Doppler ultrasound. The results showed that the NT-proBNP levels in CHF group were significantly higher than that of in the control group (P<0.05). Further, the NT-proBNP levels showed an increased tendency accompanied by the severity of heart failure (P<0.05) and lowering of LVEF (r=-0.595, P<0.05). The serum NT-proBNP levels can reflect the state of cardiac function in patients with decompensated DHF, and useful in the diagnosis and severity assessment of CHF. (authors)

  1. Prognostic usefulness of anemia and N-terminal pro-brain natriuretic peptide in outpatients with systolic heart failure

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Kistorp, Caroline N

    2007-01-01

    N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and anemia are predictors of outcome in systolic heart failure. It is currently unclear how these 2 markers interact in particular with regard to the prognostic information carried by each risk marker. We therefore tested the hypothesis...... that anemia (World Health Organization criteria, hemoglobin levels ... prospectively at the baseline visit to our heart failure clinic (inclusion criterion left ventricular ejection fraction anemia was 27%. In a multivariate logistic regression model, anemia (p = 0...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. N-terminal-pro-B type natriuretic peptide as a useful tool to evaluate pulmonary hypertension and cardiac function in CDH infants.

    Science.gov (United States)

    Baptista, Maria J; Rocha, Gustavo; Clemente, Fátima; Azevedo, Luís F; Tibboel, Dick; Leite-Moreira, Adelino F; Guimarães, Hercília; Areias, José C; Correia-Pinto, Jorge

    2008-01-01

    In congenital diaphragmatic hernia (CDH) the severity of pulmonary hypertension (PH) is considered, by several authors, determinant of clinical outcome. Plasmatic N-terminal-pro-B type natriuretic peptide (NT-proBNP) might be useful in diagnosis and management of PH in newborns, although its interest in CDH infants remains to be defined. Early NT-proBNP levels were assessed in CDH infants and correlated with cardiovascular echocardiographic parameters. 28 newborns, CDH and age-matched controls were enrolled in a prospective study. Clinical condition, NT-proBNP plasmatic levels, echo parameters of PH and biventricular function were assessed at 24 h after delivery as well as survival outcome. Estimated mean pulmonary pressure and NT-proBNP were significantly higher in CDH than control infants. NT-proBNP significantly correlated with estimated pulmonary artery pressure, right ventricular Tei index, and tricuspid E/A ratio. Additionally, we found that CDH infants with NT-proBNP >11,500 pg/ml experienced a worse prognosis. We demonstrated that PH is associated with NT-proBNP elevation and diastolic impairment in CDH infants. Early elevations in NT-proBNP levels seem to alert for a subset of CDH infants with worse prognosis. (c) 2007 S. Karger AG, Basel.

  4. N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population.

    Science.gov (United States)

    Zonneveld, Hazel I; Ikram, M Arfan; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Krestin, Gabriel P; Franco, Oscar H; Vernooij, Meike W

    2017-04-01

    Purpose To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is a marker of heart disease, and markers of subclinical brain damage on magnetic resonance (MR) images in community-dwelling middle-aged and elderly subjects without dementia and without a clinical diagnosis of heart disease. Materials and Methods This prospective population-based cohort study was approved by a medical ethics committee overseen by the national government, and all participants gave written informed consent. Serum levels of NT-proBNP were measured in 2397 participants without dementia or stroke (mean age, 56.6 years; age range, 45.7-87.3 years) and without clinical diagnosis of heart disease who were drawn from the population-based Rotterdam Study. All participants were examined with a 1.5-T MR imager. Multivariable linear and logistic regression analyses were used to investigate the association between NT-proBNP level and MR imaging markers of subclinical brain damage, including volumetric, focal, and microstructural markers. Results A higher NT-proBNP level was associated with smaller total brain volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.021; 95% confidence interval [CI]: -0.034, -0.007; P = .003) and was predominantly driven by gray matter volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.037; 95% CI: -0.057, -0.017; P < .001). Higher NT-proBNP level was associated with larger white matter lesion volume (mean difference in z score per standard deviation increase in NT-proBNP level, 0.090; 95% CI: 0.051, 0.129; P < .001), with lower fractional anisotropy (mean difference in z score per standard deviation increase in NT-proBNP level, -0.048; 95% CI: -0.088, -0.008; P = .019) and higher mean diffusivity (mean difference in z score per standard deviation increase in NT-proBNP level, 0.054; 95% CI: 0.018, 0.091; P = .004) of normal-appearing white matter

  5. Association of menopause age and N-terminal pro brain natriuretic peptide: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Ebong, Imo A; Watson, Karol E; Goff, David C; Bluemke, David A; Srikanthan, Preethi; Horwich, Tamara; Bertoni, Alain G

    2015-05-01

    Menopause age can affect the risk of developing cardiovascular disease (CVD). The purpose of this study was to investigate the associations of early menopause (menopause occurring before age 45 y) and menopause age with N-terminal pro brain natriuretic peptide (NT-proBNP), a potential risk marker of CVD and heart failure. Our cross-sectional study included 2,275 postmenopausal women, aged 45 to 85 years and without clinical CVD (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Participants were classified as having or not having early menopause. NT-proBNP was log-transformed. Multivariable linear regression was used for analysis. Five hundred sixty-one women had early menopause. The median (25th-75th percentiles) NT-proBNP value was 79.0 (41.1-151.6) pg/mL for all participants, 83.4 (41.4-164.9) pg/mL for women with early menopause, and 78.0 (40.8-148.3) pg/mL for women without early menopause. The mean (SD) age was 65 (10.1) and 65 (8.9) years for women with and without early menopause, respectively. No significant interactions between menopause age and ethnicity were observed. In multivariable analysis, early menopause was associated with a 10.7% increase in NT-proBNP levels, whereas each 1-year increase in menopause age was associated with a 0.7% decrease in NT-proBNP levels. Early menopause is associated with greater NT-proBNP levels, whereas each 1-year increase in menopause age is associated with lower NT-proBNP levels, in postmenopausal women.

  6. Performance of N-terminal-pro-B-type natriuretic peptide in critically ill patients: a prospective observational cohort study.

    Science.gov (United States)

    Coquet, Isaline; Darmon, Michael; Doise, Jean-Marc; Degrès, Michel; Blettery, Bernard; Schlemmer, Benoît; Gambert, Philippe; Quenot, Jean-Pierre

    2008-01-01

    The purpose of this study was to assess the accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) as a diagnostic tool to recognize acute respiratory failure of cardiac origin in an unselected cohort of critically ill patients. We conducted a prospective observational study of medical ICU patients. NT-proBNP was measured at ICU admission, and diagnosis of cardiac dysfunction relied on the patient's clinical presentation and echocardiography. Of the 198 patients included in this study, 102 (51.5%) had evidence of cardiac dysfunction. Median NT-proBNP concentrations were 5,720 ng/L (1,430 to 15,698) and 854 ng/L (190 to 3,560) in patients with and without cardiac dysfunction, respectively (P < 0.0001). In addition, NT-proBNP concentrations were correlated with age (rho = 0.43, P < 0.0001) and inversely correlated with creatinine clearance (rho = -0.58, P < 0.0001). When evaluating the performance of NT-proBNP concentrations to detect cardiac dysfunction, the area under the receiver operating characteristic (ROC) curve was 0.76 (95% confidence interval (CI) 0.69 to 0.83). In addition, a stepwise logistic regression model revealed that NT-proBNP (odds ratio (OR) = 1.01 per 100 ng/L, 95% CI 1.002 to 1.02), electrocardiogram modifications (OR = 11.03, 95% CI 5.19 to 23.41), and severity assessed by organ system failure score (OR = 1.63 per point, 95% CI 1.17 to 2.41) adequately predicted cardiac dysfunction. The area under the ROC curve of this model was 0.83 (95% CI 0.77 to 0.90). NT-proBNP measured at ICU admission might represent a useful marker to exclude cardiac dysfunction in critically ill patients.

  7. The N-terminal strand modulates immunoglobulin light chain fibrillogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Pozo-Yauner, Luis del, E-mail: ldelpozo@inmegen.gob.mx [Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, Delegación Tlalpan, México, D.F. C.P. 14610 (Mexico); Wall, Jonathan S. [Departments of Radiology and Medicine, The University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN (United States); González Andrade, Martín [Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, Delegación Tlalpan, México, D.F. C.P. 14610 (Mexico); Sánchez-López, Rosana [Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Col. Chamilpa Cuernavaca, Morelos C.P. 62210 (Mexico); Rodríguez-Ambriz, Sandra L. [Centro de Desarrollo de Productos Bióticos, Instituto Politécnico Nacional, Calle CEPROBI No. 8, Col. San Isidro, Yautepec, Morelos C.P. 62731 (Mexico); Pérez Carreón, Julio I. [Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, Delegación Tlalpan, México, D.F. C.P. 14610 (Mexico); and others

    2014-01-10

    Highlights: •We evaluated the impact of mutations in the N-terminal strand of 6aJL2 protein. •Mutations destabilized the protein in a position-dependent manner. •Destabilizing mutations accelerated the fibrillogenesis by shortening the lag time. •The effect on the kinetic of fibril elongation by seeding was of different nature. •The N-terminal strand is buried in the fibrillar state of 6aJL2 protein. -- Abstract: It has been suggested that the N-terminal strand of the light chain variable domain (V{sub L}) protects the molecule from aggregation by hindering spurious intermolecular contacts. We evaluated the impact of mutations in the N-terminal strand on the thermodynamic stability and kinetic of fibrillogenesis of the V{sub L} protein 6aJL2. Mutations in this strand destabilized the protein in a position-dependent manner, accelerating the fibrillogenesis by shortening the lag time; an effect that correlated with the extent of destabilization. In contrast, the effect on the kinetics of fibril elongation, as assessed in seeding experiments was of different nature, as it was not directly dependant on the degree of destabilization. This finding suggests different factors drive the nucleation-dependent and elongation phases of light chain fibrillogenesis. Finally, taking advantage of the dependence of the Trp fluorescence upon environment, four single Trp substitutions were made in the N-terminal strand, and changes in solvent exposure during aggregation were evaluated by acrylamide-quenching. The results suggest that the N-terminal strand is buried in the fibrillar state of 6aJL2 protein. This finding suggest a possible explanation for the modulating effect exerted by the mutations in this strand on the aggregation behavior of 6aJL2 protein.

  8. Exercise-induced hypoxemia: fact or fallacy?

    Science.gov (United States)

    Scroop, Garry C; Shipp, Nicholas J

    2010-01-01

    Whereas the prevalence of exercise-induced hypoxemia (EIH) in endurance athletes is commonly reported as approximately 50%, most previous studies have not corrected PaO2 for exercise-induced hyperthermia. Furthermore, although a detrimental effect on aerobic performance has been assumed, no study has measured arterial oxygen content (CaO2) in this context. To determine the effect of temperature-correcting PaO2 values for rectal, arterial blood, esophageal, and exercising muscle temperatures during exercise on CaO2 and the prevalence of EIH. Twenty-three trained males (age 26 +/- 5 yr; VO2peak 65.2 +/- 1.6 mL x kg-1 x min-1) performed incremental treadmill exercise to exhaustion with PaO2 corrected for simultaneous temperature measurements at all four sites. EIH was defined as DeltaPaO2 >or= 10 mm Hg. : With no temperature correction, DeltaPaO2 was -20.8 +/- 5.0 mm Hg and prevalence was 96% (n = 23), but when corrected for rectal temperature, DeltaPaO2 was -14.7 +/- 7.8 mm Hg and prevalence was 73% (n = 20); for arterial blood temperature, DeltaPaO2 was -7.7 +/- 6.5 mm Hg and prevalence was 35% (n = 20); and for esophageal temperature, DeltaPaO2 was -8.1 +/- 7.7 mm Hg and prevalence was 48% (n = 23), although when corrected for active muscle temperature, DeltaPaO2 was +8.2 +/- 7.8 mm Hg and prevalence was 0% (n = 10). There were no significant changes in CaO2 except for uncorrected values, and there was no correlation between DeltaPaO2 and VO2peak. Although the prevalence of EIH depends on the temperature correction applied to PaO2 values, in no case is there a significant change in CaO2 or any relationship with maximal aerobic power.

  9. Detection of left ventricular enlargement and impaired systolic function with plasma N-terminal pro brain natriuretic peptide concentrations

    DEFF Research Database (Denmark)

    Grønning, Bjørn Aaris; Nilsson, Jens C.; Søndergaard, Lars

    2002-01-01

    BACKGROUND: Brain- and N-terminal pro brain natriuretic peptide (NT-proBNP) have been identified as promising markers for heart failure. However, previous studies have revealed that they may hold insufficient diagnostic power for implementation into clinical practice because of a significant...... overlap in the range of plasma levels between healthy subjects and subjects with heart failure. We hypothesized that imprecision of the reference method (ie, the echocardiographic evaluation of left ventricular [LV] function) may have affected results from those earlier studies. We therefore wanted...... to investigate the diagnostic potential of NT-proBNP with magnetic resonance imaging as the reference method for the cardiac measurements. METHODS: Forty-eight patients with stable symptomatic heart failure in New York Heart Association functional classifications II to IV were examined once with blood samples...

  10. N-terminal pro-atrial natriuretic peptide response to acute exercise in depressed patients and healthy controls

    DEFF Research Database (Denmark)

    Krogh, Jesper; Ströhle, Andreas; Westrin, Asa

    2011-01-01

    BACKGROUND: The dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in major depression includes hyperactivity and reduced feedback inhibition. Atrial natriuretic peptide (ANP) is able to reduce the HPA-axis response to stress and has an anxiolytic effect in rodents and humans. We hypothesized...... that patients with depression would have an attenuated N-terminal proANP (NT-proANP) response to acute exercise compared to healthy controls. Secondly, we aimed to assess the effect of antidepressants on NT-proANP response to acute exercise. METHODS: We examined 132 outpatients with mild to moderate depression...... depressed subjects and healthy controls (group×time; F(4,162.9)=10.92; p...

  11. Exercise-Induced Bronchospasm and Allergy.

    Science.gov (United States)

    Caggiano, Serena; Cutrera, Renato; Di Marco, Antonio; Turchetta, Attilio

    2017-01-01

    Sport is an essential part of childhood, with precious and acknowledged positive health effects but the impact of exercise-induced bronchoconstriction (EIB) significantly reduces participation in physical activity. It is important to recognize EIB, differentiating EIB with or without asthma if the transient narrowing of the airways after exercise is associated with asthmatic symptoms or not, in the way to select the most appropriate treatment among the many treatment options available today. Therapy is prescribed based on symptoms severity but diagnosis of EIB is established by changes in lung function provoked by exercise evaluating by direct and indirect tests. Sometimes, in younger children it is difficult to obtain the registration of difference between the preexercise forced expiratory volume in the first second (FEV1) value and the lowest FEV1 value recorded within 30 min after exercise, defined as the gold standard, but interrupter resistance, in association with spirometry, has been showed to be a valid alternative in preschool age. Atopy is the main risk factor, as demonstrated by epidemiologic data showing that among the estimated pediatric population with EIB up to 40% of them have allergic rhinitis and 30% of these patients may develop adult asthma, according with atopic march. Adopting the right treatment and prevention, selecting sports with no marked hyperventilation and excessive cooling of the airways, children with EIB can be able to take part in physical activity like all others.

  12. Exercise-Induced Bronchospasm and Allergy

    Directory of Open Access Journals (Sweden)

    Serena Caggiano

    2017-06-01

    Full Text Available Sport is an essential part of childhood, with precious and acknowledged positive health effects but the impact of exercise-induced bronchoconstriction (EIB significantly reduces participation in physical activity. It is important to recognize EIB, differentiating EIB with or without asthma if the transient narrowing of the airways after exercise is associated with asthmatic symptoms or not, in the way to select the most appropriate treatment among the many treatment options available today. Therapy is prescribed based on symptoms severity but diagnosis of EIB is established by changes in lung function provoked by exercise evaluating by direct and indirect tests. Sometimes, in younger children it is difficult to obtain the registration of difference between the preexercise forced expiratory volume in the first second (FEV1 value and the lowest FEV1 value recorded within 30 min after exercise, defined as the gold standard, but interrupter resistance, in association with spirometry, has been showed to be a valid alternative in preschool age. Atopy is the main risk factor, as demonstrated by epidemiologic data showing that among the estimated pediatric population with EIB up to 40% of them have allergic rhinitis and 30% of these patients may develop adult asthma, according with atopic march. Adopting the right treatment and prevention, selecting sports with no marked hyperventilation and excessive cooling of the airways, children with EIB can be able to take part in physical activity like all others.

  13. Review of exercise-induced asthma.

    Science.gov (United States)

    Storms, William W

    2003-09-01

    The purpose of this manuscript is to review the recent literature on exercise-induced asthma (EIA) and summarize the pathogenesis, diagnosis, and treatment of this condition. A review of the English language medical literature was performed to obtain articles on EIA. The pathophysiology of EIA is not fully understood, but there are two theories: 1) the hyperosmolar theory and 2) the airway rewarming theory. In addition, there have been data to show that airway inflammation is present in some elite athletes, especially in cold weather sports. The diagnosis of EIA is usually straightforward in most patients, but a number of patients may have atypical symptoms and may be more difficult to diagnose. They may well need exercise testing or eucapnic voluntary ventilation testing. Most people respond to treatment with an inhaled beta agonist and or cromolyn before exercise, but some patients will also need other medications, including daily medications such as inhaled steroids. When treatment does not control the problem, then further diagnostic evaluation should be done to rule out conditions other than EIA, such as vocal cord dysfunction or cardiac or pulmonary problems. EIA is a condition that may occur in schoolchildren in gym class and also in Olympic athletes. The diagnosis and treatment is usually fairly straightforward, but at times it may be challenging. However, all patients should be followed to make sure that the correct diagnosis is made and to make sure that treatment is effective.

  14. NT-ProBNP Independently Predicts Long-Term Mortality in Patients Admitted for Coronary Angiography

    DEFF Research Database (Denmark)

    Ruwald, Martin Huth; Goetze, Jens Peter; Bech, Jan

    2014-01-01

    Recently, research interests are focussed on biomarkers to predict the outcome in patients with coronary artery disease (CAD). We examined whether the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict outcome in patients who underwent elective or acute coronary angiogr......-proBNP is an independent predictor of ACM on long-term follow-up. N-terminal-proBNP is a reliable predictive marker of mortality in the setting of stable or unstable angina....

  15. N-terminal pro-brain natriuretic peptide for additional risk stratification in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy

    NARCIS (Netherlands)

    Windhausen, Fons; Hirsch, Alexander; Sanders, Gerard T.; Cornel, Jan Hein; Fischer, Johan; van Straalen, Jan P.; Tijssen, Jan G. P.; Verheugt, Freek W. A.; de Winter, Robbert J.

    2007-01-01

    BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this

  16. 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....

  17. Exercise-induced phospho-proteins in skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, A S; Hawley, J A; Zierath, J R

    2008-01-01

    Efforts to identify exercise-induced signaling events in skeletal muscle have been influenced by ground-breaking discoveries in the insulin action field. Initial discoveries demonstrating that exercise enhances insulin sensitivity raised the possibility that contraction directly modulates insulin...

  18. Wheezing or Breezing through Exercise-Induced Asthma.

    Science.gov (United States)

    McCarthy, Paul

    1989-01-01

    Several physicians discuss the tests they use to diagnose exercise-induced asthma (EIA), the medications they typically prescribe and why, and the importance of properly educating athletes about EIA. (JD)

  19. Nonpharmacologic strategies to manage exercise-induced bronchoconstriction

    DEFF Research Database (Denmark)

    Dickinson, John; Amirav, Israel; Hostrup, Morten

    2018-01-01

    Pharmacologic management of exercise-induced bronchoconstriction (EIB) is the mainstay of preventative therapy. There are some nonpharmacologic interventions, however, that may assist the management of EIB. This review discusses these nonpharmacologic interventions and how they may be applied...

  20. Asthma Bronchiale and Exercise-Induced Bronchoconstriction.

    Science.gov (United States)

    Jayasinghe, Harshani; Kopsaftis, Zoe; Carson, Kristin

    2015-01-01

    Exercising regularly has a wide range of beneficial health effects; in particular, it has been well documented to help in the management of chronic illnesses including asthma. However, in some individuals, exertion can also trigger an exacerbation of asthmatic episodes and subsequent acute attacks of breathlessness, coughing, tightness of the chest and wheezing. This physiological process is called exercise-induced bronchoconstriction (EIB) whereby post-exercise forced expiratory volume in 1 s is reduced by 10-15% from baseline. While EIB is highly prevalent in asthmatics and presents with similar respiratory symptoms, asthma and EIB are not mutually exclusive. The aim of this review is to present a broad overview of both conditions in order to enhance the understanding of the similarities and differences distinguishing them as two separate entities. The pathophysiology and mechanisms underlying asthma are well described with research now focussing on defining phenotypes for targeted management strategies. Conversely, the mechanistic understanding of EIB remains largely under-described. Diagnostic pathways for both are established and similar, as are pharmacologic and non-pharmacologic treatments and management approaches, which have enhanced success with early detection. Given the potential for exacerbation of asthma, exercise avoidance is common but counterproductive as current evidence indicates that it is well tolerated and improves quality of life. Literature supporting the benefit of exercise for EIB sufferers is at present favourable, yet extremely limited; therefore, future research should be directed in this area as well as towards further developing the understanding of the pathophysiology and mechanisms underpinning both EIB and asthma. © 2015 S. Karger AG, Basel.

  1. Management of Exercise-Induced Bronchospasm in Children

    OpenAIRE

    Hendeles, Leslie; Asmus, Michael J.; Chesrown, Sarah

    2003-01-01

    Bronchospasm precipitated by exercise is often indistinguishable from bronchospasm produced by other stimuli. Symptoms result from airflow limitation and include wheezing, cough, chest tightness, dyspnea and sometimes hypoxemia. The prevalence of exercise-induced bronchospasm varies from 30%-90%, but virtually all patients with current asthma will experience a decrease in lung function if the exercise is sufficiently vigorous, especially in cold, dry environmental conditions. Exercise-induced...

  2. NT-proBNP, C-reactive protein and soluble uPAR in a bi-ethnic male population

    DEFF Research Database (Denmark)

    Kruger, Ruan; Schutte, Rudolph; Huisman, Hugo W

    2013-01-01

    This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort....

  3. Plasma N-terminal pro-brain natriuretic peptide as a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria

    DEFF Research Database (Denmark)

    Gaede, P; Hildebrandt, P; Hess, G

    2005-01-01

    AIMS/HYPOTHESIS: We examined whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) predicts cardiovascular outcome in patients with type 2 diabetes. METHODS: A total of 160 microalbuminuric type 2 diabetic patients (mean age 55.1 years [SD 7.2], 119 men) were enrolled in the Steno-2 ....../INTERPRETATION: We conclude that high plasma NT-proBNP is a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.......AIMS/HYPOTHESIS: We examined whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) predicts cardiovascular outcome in patients with type 2 diabetes. METHODS: A total of 160 microalbuminuric type 2 diabetic patients (mean age 55.1 years [SD 7.2], 119 men) were enrolled in the Steno-2......, myocardial infarction, stroke, revascularisation procedures in the heart or legs, and amputations. RESULTS: In the whole group, plasma NT-proBNP being above the median was associated with an increased risk of cardiovascular disease during follow-up, with an unadjusted hazard ratio of 4.4 (95% CI 2.3-8.4; p

  4. N-Terminal Pro-B Type Natriuretic Peptide as a Marker of Bronchopulmonary Dysplasia or Death in Very Preterm Neonates

    DEFF Research Database (Denmark)

    Sellmer, Anna; Hjortdal, Vibeke Elisabeth; Bjerre, Jesper Vandborg

    2015-01-01

    BACKGROUND: Bronchopulmonary dysplasia (BPD) is a serious complication of preterm birth. Plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) has been suggested as a marker that may predict BPD within a few days after birth. OBJECTIVES: To investigate the association between NT-proBNP day...... three and bronchopulmonary dysplasia (BPD) or death and further to assess the impact of patent ductus arteriosus (PDA) on this association in neonates born before 32 gestational weeks. METHODS: A cohort study of 183 neonates born before 32 gestational weeks consecutively admitted to the Neonatal...... Intensive Care Unit, Aarhus University Hospital, Denmark. On day three plasma samples were collected and echocardiography carried out. NT-proBNP was measured by routine immunoassays. The combined outcome BPD or death was assessed at 36 weeks of postmenstrual age. Receiver operator characteristic (ROC...

  5. NT-proBNP, echocardiographic abnormalities and subclinical coronary artery disease in high risk type 2 diabetic patients

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Hansen, Peter R; Wiinberg, Niels

    2012-01-01

    Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P......-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients...

  6. NT-proBNP is associated with fibulin-1 in Africans

    DEFF Research Database (Denmark)

    Kruger, R; Schutte, R; Huisman, H W

    2012-01-01

    , expressed in elastin-containing fibres of blood vessels, and also in the heart. Due to an alarming prevalence of hypertensive heart disease in black South Africans, we investigated the associations of NT-proBNP with fibulin-1 and markers of arterial stiffness in Africans and Caucasians.......The N-terminal prohormone B-type natriuretic peptide (NT-proBNP) is involved in the regulation of volume load and secreted when systemic cardiac overload occurs. Fibulin-1 on the other hand is a component of many extracellular matrix proteins including those present in atherosclerotic lesions...

  7. Exercise-induced asthma in asthmatic children of southern Iran.

    Science.gov (United States)

    Fayezi, Abbas; Amin, Reza; Kashef, Sara; Al Yasin, Soheila; Bahadoram, Mohammad

    2014-09-28

    Asthma is a common illness, especially among children. Exercise-induced asthma is an important consideration, both as a factor, limiting physical activity of patients, and also as an indicator of poor long term control. We investigated pre-Valence of exercise-induced asthma in a group of asthmatic children living in southern Iran. We conducted treadmill exercise challenge test in 40 young asthmatic patients aged 6 to 18. After 8 minutes exercise to achieve 80% of maximum heart rate predicted for age, patients were examined and spirometry values recorded at frequent intervals. We defined exercise-induced asthma as 10% or more decline in Forced Expiratory Volume in one second (FEV1) within 30 minutes after exercise challenge. Of 40 patients evaluated, 22 patients ( 55% of total ) met our criteria for exercise-induced asthma. Most positive responses (7 of 22, 31.8%) occurred at about 10 minutes after exercise. Cough was the most consistent sign (18 of 22 patients, 81%). In 2 patients (9%), FEV 1 decline did not accompany any symptom or sign. We concluded that Exercise- induced asthma occurs in a relatively smaller subset of southern Iranian asthmatic children. Also treadmill exercise challenge performed by a trained staff, following standard protocol and using enough monitoring and precautions is safe and diagnostic in children and adolescents.

  8. N-terminal-pro-brain natriuretic peptide, but not brain natriuretic peptide, is increased in patients with severe obesity

    Directory of Open Access Journals (Sweden)

    F. Fernandes

    2007-02-01

    Full Text Available Elevated body mass index (BMI has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP and brain natriuretic peptide (BNP and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m², mean age: 39 years were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m², mean age: 43 years. The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003 in obese patients (mean 1.67, 95% CI: 1.50-1.83 log pg/mL compared to controls (mean: 1.32, 95% CI: 1.17-1.47 log pg/mL. The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004. No difference was detected in the Log-BNP concentration (P = 0.63 of obese patients (mean: 0.73, 95% CI: 0.46-1.00 log pg/mL compared to controls (mean: 0.66, 95% CI: 0.51-0.81 log pg/mL. NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.

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

    Science.gov (United States)

    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.

  10. The N-terminal cytoplasmic region of NCBE displays features of an intrinsic disordered structure and represents a novel target for specific drug screening

    Science.gov (United States)

    Bjerregaard-Andersen, Kaare; Perdreau-Dahl, Harmonie; Guldsten, Hanne; Praetorius, Jeppe; Jensen, Jan K.; Morth, Jens P.

    2013-01-01

    The sodium dependent bicarbonate transporter NCBE/NBCn2 is predominantly expressed in the central nervous system (CNS). The highest protein concentrations are found in the choroid plexus. The primary function of this integral plasma membrane transport protein is to regulate intracellular neuronal pH and also probably to maintain the pH homeostasis across the blood-cerebrospinal fluid barrier. NCBE is predicted to contain at least 10 transmembrane helices. The N- and C- termini are both cytoplasmic, with a large N-terminal domain (Nt-NCBE) and a relatively small C-terminal domain (Ct-NCBE). The Nt-NCBE is likely to be involved in bicarbonate recognition and transport and contains key areas of regulation involving pH sensing and protein-protein interactions. Intrinsic disordered protein regions (IDPRs) are defined as protein regions having no rigid three-dimensional structure under physiological conditions. They are believed to be involved in signaling networks in which specific, low affinity, protein-protein interactions play an important role. We predict that NCBE and other SoLute Carrier 4 (SLC4) family members have a high level of intrinsic disorder in their cytoplasmic regions. To provide biophysical evidence for the IDPRs predicted in Nt-NCBE, we produced pure (>99%), recombinant Nt-NCBE using E. coli as the expression host. The protein was used to perform differential scanning fluorescence spectroscopy (DSF), in order to search for small molecules that would induce secondary or tertiary structure in the IDPRs. We expect this to assist the development of selective pharmaceutical compounds against individual SLC4 family members. We have also determined a low resolution (4 Å) X-ray crystal structure of the N-terminal core domain. The N-terminal cytoplasmic domain (cdb3) of anion exchanger 1 (AE1) shares a similar fold with the N-terminal core domain of NCBE. Crystallization conditions for the full-length N-terminal domain have been sought, but only the core

  11. Detection of titin fragments in urine in response to exercise-induced muscle damage.

    Directory of Open Access Journals (Sweden)

    Kazue Kanda

    Full Text Available Many studies have attempted to determine the associations between blood biomarkers and exercise-induced muscle damage. However, poor correlations between the changes in biomarker levels and the magnitude of muscle symptoms have been reported. Recent advances in proteomic tools offer a strategy for the comprehensive analysis of protein expression, which can be used to identify biomarkers. Here, we used a proteomic analysis to identify urinary proteins that appear in response to a calf-raise exercise, including repetitive eccentric muscle contractions, and found that a titin (also known as connectin N-terminal fragment molecule appears in the urine after eccentric exercise. We measured the titin fragment in urine samples from nine individuals before and after eccentric exercise using a newly-established enzyme-linked immunosorbent assay and found that the titin fragment excretion rate increased 96 h after the exercise (5.1 to 77.6 pg/min, p <0.01. The changes in the titin fragment excretion rate were correlated strongly with blood markers of muscle damage and with muscle symptoms. These findings suggest that the urinary titin fragment is potentially a noninvasive biomarker of muscle damage.

  12. Cardiac involvement in myotonic dystrophy: The role of troponins and N-terminal pro B-type natriuretic peptide.

    Science.gov (United States)

    Valaperta, Rea; De Siena, Claudia; Cardani, Rosanna; Lombardia, Fortunata; Cenko, Edina; Rampoldi, Benedetta; Fossati, Barbara; Brigonzi, Elisa; Rigolini, Roberta; Gaia, Paola; Meola, Giovanni; Costa, Elena; Bugiardini, Raffaele

    2017-12-01

    Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are dominant inherited muscular dystrophies with multiple systemic involvement, often producing cardiac injury. This study sought to determine the clinical significance of elevated high sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI), and N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in this population. Sixty DM patients (35 men and 25 women; mean age: 45.1 years, range: 12-73 years) underwent clinical cardiac investigations and measurements of serum hs-cTnT, hs-cTnI, creatine kinase (CK), and NT-proBNP. Left ventricular (LV) ejection fraction (EF) was assessed by echocardiography. Genetic analysis revealed that 46 of the 60 patients were DM1, and 14 DM2. Blood measurements showed persistent elevation of hs-cTnT and CK in 55/60 DM patients (91.73%). In contrast, hs-cTnI values were persistently normal throughout the study. Only 2 patients showed an EF 125 pg/mL was an independent predictor of ECG abnormalities. NT-pro-BNP levels may be considered to be used clinically to identify DM patients at increased risk of developing myocardial conduction abnormalities. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Exercise-induced bronchoconstriction in Tunisian elite athletes is underdiagnosed

    Directory of Open Access Journals (Sweden)

    Sallaoui R

    2011-06-01

    Full Text Available Ridha Sallaoui1–3, Ines Zendah2, Habib Ghedira2, Mohcine Belhaouz3, Mourad Ghrairi3, Mohamed Amri31Issep Sfax, Unité de Recherche “Les déterminants psychoculturels et biologiques de l'accès à la haute performance sportive,” Sfax; 2Department of Lung Function Testing, Abderrahmen Mami Pneumo-Allergology Hospital, Department III, Tunis, Tunisia; 3Laboratoire de Physiologie de la Nutrition, Faculté des Sciences de Tunis, El Manar 1060 Tunis, TunisiaAbstract: Many studies have shown an increased risk of developing exercise-induced bronchoconstriction among the athletic population, particularly at the elite level. Subjective methods for assessing exercise-induced bronchoconstriction such as surveys and questionnaires have been used but have resulted in an underestimation of the prevalence of airway dysfunction when compared with objective measurements. The aim of the present study was to compare the prevalence of exercise-induced bronchoconstriction among Tunisian elite athletes obtained using an objective method with that using a subjective method, and to discuss the possible causes and implications of the observed discrepancy. As the objective method we used spirometry before and after exercise and for the subjective approach we used a medical history questionnaire. All of the recruited 107 elite athletes responded to the questionnaire about respiratory symptoms and medical history and underwent a resting spirometry testing before and after exercise. Post-exercise spirometry revealed the presence of exercise-induced bronchoconstriction in 14 (13% of the elite athletes, while only 1.8% reported having previously been diagnosed with asthma. In conclusion, our findings indicate that medical history-based diagnoses of exercise-induced bronchoconstriction lead to underestimations of true sufferers.Keywords: exercise-induced bronchoconstriction, elite athletes, self-reported asthma

  14. N-terminal pro-B-type natriuretic peptide as a marker of blunt cardiac contusion in trauma

    Science.gov (United States)

    Dogan, Halil; Sarikaya, Sezgin; Neijmann, Sebnem Tekin; Uysal, Emin; Yucel, Neslihan; Ozucelik, Dogac Niyazi; Okuturlar, Yıldız; Solak, Suleyman; Sever, Nurten; Ayan, Cem

    2015-01-01

    Cardiac contusion is usually caused by blunt chest trauma and, although it is potentially a life-threatening condition, the diagnosis of a myocardial contusion is difficult because of non-specific symptoms and the lack of an ideal test to detect myocardial damage. Cardiac enzymes, such as creatine kinase (CK), creatine kinase MB fraction (CK-MB), cardiac troponin I (cTn-I), and cardiac troponin T (cTn-T) were used in previous studies to demonstrate the blunt cardiac contusion (BCC). Each of these diagnostic tests alone is not effective for diagnosis of BCC. The aim of this study was to investigate the serum heart-type fatty acid binding protein (h-FABP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), CK, CK-MB, and cTn-I levels as a marker of BCC in blunt chest trauma in rats. The eighteen Wistar albino rats were randomly allocated to two groups; group I (control) (n=8) and group II (blunt chest trauma) (n=10). Isolated BCC was induced by the method described by Raghavendran et al. (2005). All rats were observed in their cages and blood samples were collected after five hours of trauma for the analysis of serum h-FABP, NT-pro BNP, CK, CK-MB, and cTn-I levels. The mean serum NT-pro BNP was significantly different between group I and II (10.3±2.10 ng/L versus 15.4±3.68 ng/L, respectively; P=0.0001). NT-pro BNP level >13 ng/ml had a sensitivity of 87.5%, a specificity of 70%, a positive predictive value of 70%, and a negative predictive value of 87.5% for predicting blunt chest trauma (area under curve was 0.794 and P=0.037). There was no significant difference between two groups in serum h-FABP, CK, CK-MB and c Tn-I levels. A relation between NT-Pro BNP and BCC was shown in this study. Serum NT-proBNP levels significantly increased with BCC after 5 hours of the blunt chest trauma. The use of NT-proBNP as an adjunct to other diagnostic tests, such as troponins, electrocardiography (ECG), chest x-ray and echocardiogram may be beneficial for diagnosis of BCC

  15. Early trends in N-terminal pro-brain natriuretic peptide values after left ventricular assist device implantation for chronic heart failure.

    Science.gov (United States)

    Hasin, Tal; Kushwaha, Sudhir S; Lesnick, Timothy G; Kremers, Walter; Boilson, Barry A; Schirger, John A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Jaffe, Allan S

    2014-10-15

    Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. cyclooxygenase inhibitors and the exercise-induced stress response

    African Journals Online (AJOL)

    homeostatic shift intended to facilitate the demands put on the body by physical exertion. Most stressors, including ... nervous system response7 and in the increase in body tem- perature and other metabolic adaptations.14 ... cyclooxygenase-1 (COX-1) in the exercise-induced cortisol and temperature response to exercise.

  17. The prevalence of exercise-induced asthma among school children ...

    African Journals Online (AJOL)

    Exercise-induced asthma (EIA) is one of the major factors that affect optimal performance in sport. The prevalence of EIA is reported to be on the increase among school children worldwide. The aim of this study was to indicate EIA prevalence among primary-school children in South Africa. A field study determined the ...

  18. BMI predicts exercise induced bronchoconstriction in asthmatic boys

    NARCIS (Netherlands)

    van Veen, Wilma J.; Driessen, Jean M. M.; Kersten, Elin T. G.; van Leeuwen, Janneke C.; Brusse-Keizer, Marjolein G. J.; van Aalderen, Wim M. C.; Thio, Bernard J.

    2017-01-01

    BackgroundExercise induced bronchoconstriction (EIB) is a frustrating morbidity of asthma in children. Obesity has been associated with asthma and with more severe EIB in asthmatic children. ObjectivesTo quantify the effect of BMI on the risk of the occurrence of EIB in children with asthma.

  19. EXERCISE-INDUCED PULMONARY HEMORRHAGE AFTER RUNNING A MARATHON

    Science.gov (United States)

    We report on a healthy 26-year-old male who had an exercise-induced pulmonary hemorrhage (EIPH) within 24 hours of running a marathon. There were no symptoms, abnormalities on exam, or radiographic infiltrates. He routinely participated in bronchoscopy research and the EIPH was e...

  20. BMI predicts exercise induced bronchoconstriction in asthmatic boys

    NARCIS (Netherlands)

    van Veen, Wilma J.; Driessen, Jean M. M.; Kersten, Elin T. G.; van Leeuwen, Janneke C.; Brusse-Keizer, Marjolein G. J.; van Aalderen, Wim M. C.; Thio, Bernard J.

    Background: Exercise induced bronchoconstriction (EIB) is a frustrating morbidity of asthma in children. Obesity has been associated with asthma and with more severe EIB in asthmatic children. Objectives: To quantify the effect of BMI on the risk of the occurrence of EIB in children with asthma.

  1. Coping with Exercise-Induced Asthma in Sports.

    Science.gov (United States)

    Katz, Roger M.

    1987-01-01

    This article reviews the history of research on exercise-induced asthma (EIA) and the pathophysiology of the condition, including its development and influencing factors. Four groups of drugs that are effective against EIA--theopyhlline, beta-adrenergic agents, cromolyn sodium, and anticholinergics--are discussed. (Author/CB)

  2. Exercise-induced respiratory symptoms not due to asthma.

    Science.gov (United States)

    Pandit, Chetan A; Batterby, Eugenie; Van Asperen, Peter; Cooper, Peter; Selvadurai, Hiran; Fitzgerald, Dominic A

    2014-10-01

    This manuscript describes two interesting patients who had exercise-induced symptoms that unmasked an alternative underlying diagnosis. The first is an 8-year-old boy who was treated for asthma all his life but really had exercise-induced stridor (labelled as wheeze) causing significant exercise limitation, which was due to a double aortic arch with the right arch compressing the trachea. The second case describes the diagnosis of vocal cord dysfunction in a 13-year-old anxious high achiever. He also initially had exercise-induced symptoms treated as exercise-induced wheeze but again had a stridor due to vocal cord dysfunction. Both these cases demonstrate the importance of detailed history including during exercise, which can unmask alternative diagnosis. Another important message is that if there is no response to bronchodilator treatment with absence of typical signs and symptoms of asthma, alternative diagnosis should be considered. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  3. Diagnosis and Management of Exercise-Induced Asthma.

    Science.gov (United States)

    Rupp, Ned T.

    1996-01-01

    Exercise-induced asthma (EIA) affects 12-15% of the population. This comprehensive guide suggests that nearly all individuals with EIA can be active, highlighting both pharmacologic and nonpharmacologic management of asthma and stressing the importance of rigorous patient education in controlling underlying asthma and EIA. (SM)

  4. Cyclooxygenase inhibitors and the exercise-induced stress response

    African Journals Online (AJOL)

    steroidal anti-inflammatory drug (NSAID) naproxen, and of the coxib, rofecoxib, on the exercise-induced stress response. Design. Eight subjects (age 20.9 ± 1.1 years, weight 70.4 ± 3.9 kg, height 170.9 ± 6.7 cm, body surface area 1.82 ± 0.09 m2, ...

  5. Exercise-Induced Bronchospasm among School Children in Gusau ...

    African Journals Online (AJOL)

    One of these, the Exercise-Induced Bronchospasm (EIB) which is a reduction in post exercise Peak Expiratory Flow Rate (PEFR), is widely used to define childhood asthma in epidemiological studies. To determine the current prevalence of asthma in childhood in a Northwestern Nigerian town, pupils aged 5–14years were ...

  6. N-terminal pro-brain natriuretic peptide can be an adjunctive diagnostic marker of hyper-acute phase of Kawasaki disease.

    Science.gov (United States)

    Kwon, Hyuksool; Lee, Jin Hee; Jung, Jae Yun; Kwak, Young Ho; Kim, Do Kyun; Jung, Jin Hee; Chang, Ikwan; Kim, Kyuseok

    2016-12-01

    The purpose of this study was to determine whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level could be a useful marker for Kawasaki disease in the pediatric emergency department (PED) and in the presence of fever duration of 4 days or less (hyper-acute phase of Kawasaki disease). Medical records of patients who were 1 month to 15 years old of age and presented at the PED with suspected Kawasaki disease from January 1, 2010, to December 31, 2014, were collected retrospectively. Two hundred thirty-nine patients with a history of fever for 4 days or less were diagnosed with Kawasaki disease, as well as 111 patients with other febrile diseases, and were enrolled. The NT-proBNP level was significantly higher in patients with Kawasaki disease (Kawasaki disease vs. other febrile disease group, 444.8 (189.7-951.5) vs. 153.4 (68.9-287.6) pg/mL; p Kawasaki disease was 0.763 (95 % CI 0.712-0.814). NT-proBNP might be an adjunctive laboratory marker for hyper-acute phase of Kawasaki disease in the PED. What is Known: • N-terminal pro-brain natriuretic peptide level has been reported as a useful marker for diagnosis in patients with the acute phase of Kawasaki disease. • But, in the cases of less than 5 days of fever, the appropriate level of NT-proBNP for differentiating Kawasaki disease in PED has not been yet evaluated. What is New: • NT-proBNP might be an adjunctive laboratory marker for hyper-acute phase of Kawasaki disease.

  7. Exercise-induced Protein Arginine Methyltransferase Expression in Skeletal Muscle.

    Science.gov (United States)

    Vanlieshout, Tiffany L; Stouth, Derek W; Tajik, Tania; Ljubicic, Vladimir

    2018-03-01

    This study aimed to determine protein arginine methyltransferase 1 (PRMT1), -4 (also known as coactivator-associated arginine methyltransferase 1 [CARM1]), and -5 expression and function during acute, exercise-induced skeletal muscle remodeling in vivo. C57BL/6 mice were assigned to one of three experimental groups: sedentary, acute bout of exercise, or acute exercise followed by 3 h of recovery. Mice in the exercise groups performed a single bout of treadmill running at 15 m·min for 90 min. Hindlimb muscles were collected, and quantitative real-time polymerase chain reaction and Western blotting were used to examine exercise-induced gene expression. The PRMT gene expression and global enzyme activity were muscle-specific, generally being higher (P < 0.05) in slow, oxidative muscle, as compared with faster, more glycolytic tissue. Despite the significant activation of canonical exercise-induced signaling involving AMP-activated protein kinase and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), PRMT expression and activity at the whole muscle level were unchanged. However, subcellular analyses revealed a significant exercise-evoked myonuclear translocation of PRMT1 before the nuclear accumulation of PGC-1α. Acute physical activity also augmented (P < 0.05) the targeted methyltransferase activities of the PRMT in the myonuclear compartment, suggesting that PRMT-mediated histone arginine methylation is part of the early signals that drive muscle plasticity. Finally, basal PGC-1α asymmetric dimethylarginine status, as well as constitutive interactions between PGC-1α and PRMT1 or CARM1 may contribute to the exercise-induced muscle remodeling process. The present study provides the first evidence that PRMT activity is selectively augmented during the initial activation of exercise-induced skeletal muscle remodeling in vivo. These data support the emergence of PRMTs as important players in the regulation of skeletal muscle plasticity.

  8. [Prediction of the risk of coronary arterial lesions in Kawasaki disease by N-terminal pro-brain natriuretic peptide].

    Science.gov (United States)

    Huiling, Lu; Yaping, Liu; Xiufen, Hu

    2015-04-01

    To detect plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) and analyze the relationship between NT-proBNP and other bio-markers in order to evaluate if NT-proBNP could be as a useful diagnostic marker to predict the risk of coronary arterial lesions in acute KD. Totally 106 patients with KD were recruited from January 2012 to April 2014 at Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology,64 were boys and 42 were girls, their age ranged from 2 months to 8 years and 4 months. Of the 106 cases, 48 had typical KD(TKD) and 58 incomplete KD(IKD). They were divided into two groups according to echocardiography results: coronary arterial lesions (KD-CAL, n = 33) and non coronary arterial lesions (KD-nCAL, n = 73). Forty children whose age and gender matched with respiratory tract infection were selected as control group, 22 were boys and 18 were girls, age range from 7 months to 7 years and 11 months. Plasma NT-proBNP levels were measured by using the enzyme-linked fluorescence analysis (ELFA) at the day of admission, meanwhile blood routine tests, liver function tests, determination of C-reactive protein (CEP), erythrocyte sedimentation rate (ESR), electrolytes were performed in these patients. Pearson's correlation analysis was used to evaluate the association. The ROC curve analysis was done to identify the threshold of coronary 'arterial lesions. The levels of NT-proBNP were (1 037 271) ng/L in TKD group and (1,325 ± 264) ng/L in IKD group. The levels of NT-proBNP in control group was (125 ± 22) ng/L. Both the levels of NT-proBNP in TKD and IKD group were significantly higher than that of control group (t = 3.360, 3.590; P blood cell count, neutrophil percentage, platelet count, CRP and ESR of KD-CAL group were significantly higher than those of the control group, however there was no significant difference between KD-CAL group and KD-nCAL group

  9. 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.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  11. N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations-Results From TIME-CHF.

    Science.gov (United States)

    Davarzani, Nasser; Sanders-van Wijk, Sandra; Karel, Joël; Maeder, Micha T; Leibundgut, Gregor; Gutmann, Marc; Pfisterer, Matthias E; Rickenbacher, Peter; Peeters, Ralf; Brunner-la Rocca, Hans-Peter

    2017-05-01

    Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies evaluated only time to first event. N-Terminal B-type natriuretic peptide (NT-proBNP)-guided therapy has not convincingly been shown to improve HF-specific outcomes, and effects on recurrent all-cause hospitalization are uncertain. Therefore, we investigated the effect of NT-proBNP-guided therapy on recurrent events in HF with the use of a time-between-events approach in a hypothesis-generating analysis. The Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized 499 HF patients, aged ≥60 years, left ventricular ejection fraction ≤45%, New York Heart Association functional class ≥I,I to NT-proBNP-guided versus symptom-guided therapy for 18 months, with further follow-up for 5.5 years. The effect of NT-proBNP-guided therapy on recurrent HF-related and all-cause hospitalizations and/or all-cause death was explored. One hundred four patients (49 NT-proBNP-guided, 55 symptom-guided) experienced 1 and 275 patients (133 NT-proBNP-guided, 142 symptom-guided) experienced ≥2 all-cause hospitalization events. Regarding HF hospitalization, 132 patients (57 NT-proBNP-guided, 75 symptom-guided) experienced 1 and 122 patients (57 NT-proBNP-guided, 65 symptom-guided) experienced ≥2 events. NT-proBNP-guided therapy was significant in preventing 2nd all-cause hospitalizations (hazard ratio [HR] 0.83; P = .01), in contrast to nonsignificant results in preventing 1st all-cause hospitalization events (HR 0.91; P = .35). This was not the case regarding HF hospitalization events (HR 0.85 [P = .14] vs HR 0.73 [P = .01]) The beneficial effect of NT-proBNP-guided therapy was seen only in patients aged <75 years, and not in those aged ≥75 years (interaction terms with P = .01 and P = .03 for all-cause hospitalization and HF hospitalization events, respectively). NT-proBNP-guided therapy

  12. N-terminal Pro-Brain Natriuretic Peptide and Exercise Capacity in Chronic Heart Failure: Data from the HF-ACTION Study

    Science.gov (United States)

    Felker, G. Michael; Whellan, David; Kraus, William E.; Clare, Robert; Zannad, Faiez; Donahue, Mark; Adams, Kirkwood; McKelvie, Robert; Piña, Ileana L; O’Connor, Christopher M.

    2013-01-01

    Objectives To examine the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure. Background Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied. Methods We analyzed the relationship between baseline NT-proBNP and peak VO2 or distance in the 6 minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak VO2 or distance in the 6 minute walk test in the context of other clinical variables. Receiver operator curve (ROC) analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak VO2 < 12 mL/kg/min. Results NT-proBNP was the most powerful predictor of peak VO2 (partial R2=0.13, p<0.0001) out of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6 minute walk test, this relationship was weaker than that for peak VO2 (partial R2 = 0.02, p<0.0001). For both peak VO2 and distance in the 6 minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. ROC analysis suggested NT-proBNP had moderate ability to identify patients with peak VO2 < 12 mL/kg/min (c-index=0.69). Conclusions In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak VO2 and a significant predictor of distance in the 6 minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak VO2 who might be considered for cardiac transplantation. These data suggest that, while hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic variables. PMID:19782787

  13. N-terminal pro-brain natriuretic peptide is related with coronary flow velocity reserve and diastolic dysfunction in patients with asymmetric hypertrophic cardiomyopathy.

    Science.gov (United States)

    Tesic, Milorad; Seferovic, Jelena; Trifunovic, Danijela; Djordjevic-Dikic, Ana; Giga, Vojislav; Jovanovic, Ivana; Petrovic, Olga; Marinkovic, Jelena; Stankovic, Sanja; Stepanovic, Jelena; Ristic, Arsen; Petrovic, Milan; Mujovic, Nebojsa; Vujisic-Tesic, Bosiljka; Beleslin, Branko; Vukcevic, Vladan; Stankovic, Goran; Seferovic, Petar

    2017-10-01

    The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP. In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP. Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  14. Plasma N-terminal pro-brain natriuretic peptide levels in patients with acute myocardial infarction, unstable angina pectoris and non-insulin-dependent diabetes

    International Nuclear Information System (INIS)

    Zhang Yonggang; Li Yuguang

    2004-01-01

    Objective: Determination of plasma N-terminal pro-brain natriuretic peptide [NT-proBNP (1-76)] levels is useful for the diagnosis of heart failure. Present study was to investigate the significance of changes of plasma NT-proBNP (1-76) levels in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP) and non-insulin-dependent diabetes (NIDD). Methods: Plasma NT-proBNP (1-76) levels were determined with RIA in 32 patients with AMI, 27 patients with UAP, 12 patients with NIDD and 20 controls. Moreover, 16 of the 32 AMI patients underwent percutaneous transluminal coronary angioplasty (PTCA) and plasma (1-76) levels were again determined 12hr before and 12hr after the procedure. Results: The plasma NT-proBNP (1-76) levels in controls were 360.8 ± 57.3 pg/ ml with no significant difference between the sexes. In patients with AMI, UAP and NIDD, NT-proBNP (1-76) levels were 554.1 ± 195.9 pg/ml, 525.7 ± 199.1 pg/ml and 552.6 ± 141.9 pg/ml respectively; all of them were significantly higher than those in controls (P 0.05). Conclusion: The plasma NT-proBNP (1-76) levels in patients with AMI, UAP and NIDD were increased significantly and the result suggested that NT-proBNP (1-76) might be a useful risk marker for these diseases. (authors)

  15. Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

    Science.gov (United States)

    Martínez-Quintana, Efrén; Marrero-Negrín, Natalia; Gopar-Gopar, Silvia; Rodríguez-González, Fayna

    2017-06-01

    Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients. © 2017, Wiley Periodicals, Inc.

  16. N-Terminal Pro-B-Type Natriuretic Peptide Levels Inversely Correlated With Heart Rate Variability in Patients With Unstable Angina Pectoris.

    Science.gov (United States)

    Dufang, Ma; Yongcheng, Wang; Ping, Jiang; Yonghui, Yin; Xiao, Li

    2016-05-25

    We explored the relationships between heart rate variability (HRV) and levels of N-terminal Pro-B-type natriuretic peptide (NT-proBNP) in patients with unstable angina pectoris (UA).A total of 90 consecutive patients admitted 100 ms (P = 0.003). With increasing levels of NT-proBNP, both the 24hour monitoring HRV and night-monitoring HRV showed that SDNN and VLF gradually decreased (P < 0.01), and patients in the NT-proBNP lowest tertile group had higher LF values than the other two groups (P < 0.05); however, no difference was found in RMSSD, HF, and TP. During the daytime, the LF, VLF, and TP values were lower in the NTproBNP highest group compared with the lowest tertile group (P < 0.05). NT-proBNP levels correlated negatively with SDNN (r = -0.314, P = 0.003) and VLF (r = -0.397, P < 0.001) but not with other HRV parameters. Multiple regression analysis showed that serum levels of NT-proBNP remained predictive of SDNN (β = -0.060, P = 0.001) and VLF (β = -0.145, P < 0.001), even after adjustment for confounders.Our study showed that the elevated serum levels of NT-proBNP predict reduced HRV parameters, and the increased NT-proBNP levels combined with decreased HRV represent the degree of neurohormonal dysfunction and may be better prognostic predictors for risk stratification in UA patients.

  17. High N-terminal pro-B-type natriuretic peptide levels are associated with reduced heart rate variability in acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Luc Lorgis

    Full Text Available AIM: We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP in patients with acute myocardial infarction (MI. METHODS AND RESULTS: The mean of standard deviation of RR intervals (SDNN, the percentage of RR intervals with >50 ms variation (pNN50, square root of mean squared differences of successive RR intervals (rMSSD, and frequency domain parameters (total power (TP, high frequency and low frequency power ratio (LF/HF were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche was measured from blood samples taken on admission. The median (IQR Nt-proBNP level was 681(159-2432 pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = -0.19, p<0.001, LF/HF (r = -0.37, p<0.001, and LF (r = -0.29, p<0.001 but not HF (r = -0.043, p = 0.172. Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE = -0.065(0.015, p<0.001, even after adjustment for confounders. CONCLUSIONS: In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI.

  18. Urine albumin/creatinine ratio, high sensitivity C-reactive protein and N-terminal pro brain natriuretic peptide--three new cardiovascular risk markers--do they improve risk prediction and influence treatment?

    DEFF Research Database (Denmark)

    Olsen, Michael H; Sehestedt, Thomas; Lyngbaek, Stig

    2010-01-01

    a larger subgroup of 16% with high cardiovascular risk in which primary prevention may be advised despite low-moderate cardiovascular risk based on HeartScore. Furthermore, combined use of high UACR or high Nt-proBNP in subjects with known cardiovascular disease or diabetes identified a large subgroup......In order to prioritize limited health resources in a time of increasing demands optimal cardiovascular risk stratification is essential. We tested the additive prognostic value of 3 relatively new, but established cardiovascular risk markers: N-terminal pro brain natriuretic peptide (Nt...

  19. Exercise-induced inspiratory symptoms in school children

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Phillipsen, Lue Drasbaek; Hjuler, Thomas

    2016-01-01

    BACKGROUND AND AIMS: Exercise-induced inspiratory symptoms (EIIS) have multiple causes, one of which is exercise-induced laryngeal obstruction (EILO). There is limited knowledge regarding EIIS in children, both in primary care practices and in pediatric asthma clinics. The aim of this study...... was to describe the feasibility of a diagnostic methodology and its results in a cohort of children with EIIS referred to our tertiary pediatric pulmonary center. METHODS: This study analyzed consecutively collected data in children from East Denmark and Greater Copenhagen referred during a 3½ years period....... The continuous laryngoscopy exercise (CLE) test directly visualizes the larynx using a flexible laryngoscope during a maximal exercise test. A post-test questionnaire evaluated the subjective impact of the examination. RESULTS: The study included 60 children (37 girls/23 boys) with a mean age of 14 years (range...

  20. High Prevalence of Exercise-Induced Laryngeal Obstruction in Athletes

    DEFF Research Database (Denmark)

    Walsted Nielsen, Emil; Hull, James H; Backer, Vibeke

    2013-01-01

    INTRODUCTION: Unexplained respiratory symptoms reported by athletes are often incorrectly considered secondary to exercise-induced asthma. We hypothesised that this may be related to exercise induced laryngeal obstruction (EILO). This study evaluates the prevalence of EILO in an unselected cohort...... of athletes. METHODS: We retrospectively reviewed the prevalence of EILO in a cohort of athletes (n=91) referred consecutively during a two-year period for asthma work-up including continuous laryngoscopy during exercise (CLE) testing. We compared clinical characteristics and bronchial hyper......-one percent of athletes with EILO and negative bronchoprovocation and bronchodilator reversibility tests used regular asthma medication at referral. CONCLUSION: In athletes with unexplained respiratory symptoms, EILO is an important differential diagnosis not discerned from other aetiologies by clinical...

  1. Elevated NT-proBNP and coronary calcium score in relation to coronary artery disease in asymptomatic type 2 diabetic patients with elevated urinary albumin excretion rate

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Hansen, Peter R; Persson, Frederik

    2011-01-01

    Elevated plasma N-terminal (NT)-proBNP levels and coronary calcium score (CCS) not only predicts myocardial ischaemia and coronary artery stenosis but also adverse cardiovascular events and mortality in type 2 diabetic patients with an increased urinary albumin excretion rate (UAER), whereas low...

  2. 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......). MATERIALS AND METHODS: A total of 242 subjects referred for diagnostic evaluation of possible CAD had blood samples obtained before, 5 min after, and again 20 h after a symptom-limited exercise test. RESULTS: Totally 40 subjects had CAD with ≥ 50% stenosis, 115 subjects had no stenosis and 87 subjects...... similarly after exercise in CAD-subjects, non-CAD-subjects, and controls (median increase 8.14 ng/L) and the increase was positively associated with baseline NT-pro-BNP but not presence of CAD. Median baseline cTnT was 6.25 ng/L in CAD-subjects and 3.00 ng/L in non-CAD-subjects as well as controls, both p...

  3. Relationship between N-terminal pro-B type natriuretic peptide and extensive echocardiographic parameters in mild to moderate aortic stenosis

    Directory of Open Access Journals (Sweden)

    Cemri M

    2008-01-01

    Full Text Available Context: The N-terminal pro-B type natriuretic peptide levels (NT pro-BNP are increased in cases of volume or pressure overload. Aims: To examine NT pro-BNP levels and enclose whether any relationship is present between the levels of NT pro-BNP and extensive echocardiographic parameters in asymptomatic patients with mild to moderate aortic stenosis (AS. Settings and Design: A cross-sectional study about the NT pro-BNP levels was conducted in 37 asymptomatic AS patients and compared with 40 controls. Methods: Patients < 70 years old with mild to moderate AS with a peak transaortic gradient> 20 mm Hg in transthoracic echocardiogram were included in our study. Extensive echocardiographic parameters and NT pro-BNP levels were obtained from these patients and these indices were compared with the control population selected from the patients who had similar clinical characteristics with the AS patients. Statistical Analysis: NT-proBNP values were found to be distribution free. Spearman correlation coefficient was used for correlation analysis. Mean values were compared by the Kruskal-Wallis test. Results: The NT pro-BNP levels were increased in patients with AS (median; interquartiles range: 686 [449-855] pg/mL vs. 140 [116-150] pg/mL, P < 0.001. Among patients with AS, when correlation analysis was performed mean transaortic gradient, aortic valve area index, myocardial performance index, E m /A m ratio, left-ventricular mass index (LVMI and E/E m ratio had correlations (r=0.38, P = 0.026; r=-0.46, P =0.008; r=0.19, P =0,049; r=-0.22, P =0.04, r=0.49, P =0.003 and r=0.53, P < 0.001 respectively with plasma NT pro-BNP levels. The LVMI (r = 0.49, P = 0.003 and E/E m ratio (r = 0.53 P < 0.001 have the strongest correlations when compared to other parameters. Conclusion: Plasma NT pro-BNP levels are increased in even asymptomatic patients with AS and correlated with several echocardiographic parameters related to severity of AS and degree of diastolic

  4. N-Terminal Pro-B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study.

    Science.gov (United States)

    Januzzi, James L; Chen-Tournoux, Annabel A; Christenson, Robert H; Doros, Gheorghe; Hollander, Judd E; Levy, Phillip D; Nagurney, John T; Nowak, Richard M; Pang, Peter S; Patel, Darshita; Peacock, W Franklin; Rivers, E Joy; Walters, Elizabeth L; Gaggin, Hanna K

    2018-03-20

    Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF. Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13). In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Hospitalization and medical cost of patients with elevated serum N-terminal pro-brain natriuretic peptide levels.

    Directory of Open Access Journals (Sweden)

    Toshiro Kitagawa

    Full Text Available Patients with heart failure (HF are reportedly at high risk for 'all-cause' re-hospitalization. A biomarker for HF, N-terminal pro-brain natriuretic peptide (NT-proBNP, enables to simply detect patients with possible HF (pHF. We examined the hospitalization and medical cost of Japanese patients detected by an elevated serum NT-proBNP, and also evaluated the effects of institutional team approaches for HF on their all-cause hospitalizations.We retrospectively extracted all adult patients with serum NT-proBNP ≥400 pg/ml measured between January and March 2012 in Hiroshima University Hospital as pHF-positive patients. We studied their all-cause hospitalization records during the past 3-year period. We also extracted all pHF-negative patients with NT-proBNP <400 pg/ml and studied as well. In the pHF-positive patients followed for 3 years after starting interprofessional team approaches to prevent the onset and exacerbation of HF in the hospital, we compared the hospitalization and medical cost between the 3-year periods before and after the start of the team approaches.We enrolled 432 pHF-positive and 485 pHF-negative patients with one or more hospitalization records. Compared to the pHF-negative patients, the pHF-positive patients had longer total hospitalization days (median [interquartile range], 30 [13-58] versus. 18 [8-39], p <0.0001 and higher total medical cost for hospitalizations (2.42 [1.07-5.08] versus. 1.80 [0.79-3.65] million yen, p <0.0001. A subset of 303 pHF-positive patients was followed for 3 years after starting the team approaches, and we found that both total hospitalization days (30 [13-57] to 8 [0-31] and medical cost for hospitalizations (2.59 [1.37-5.05] to 0.76 [0-2.38] million yen showed marked reduction in them.Patients with an elevated serum NT-proBNP have longer hospitalizations and higher costs for all-cause hospitalizations than those without. Institutional team approaches for HF may reduce them.

  6. 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

  7. NT-pro-BNP is an independent predictor of mortality in patients with end-stage renal disease

    DEFF Research Database (Denmark)

    Svensson, M.; Gorst-Rasmussen, Anders; Schmidt, Erik Berg

    2009-01-01

    Aim: Patients with end-stage renal disease (ESRD) have an increased mortality from cardiovascular disease (CVD). N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is an independent predictor of mortality in patients with ischemic heart disease and congestive heart failure. Previous data have...... followed for a median of 314 days (interquartile range 179 - 530). Using Cox regression analysis, age, female sex, systolic blood pressure, dialysis efficiency and plasma levels of NT-pro-BNP were independent prognostic risk factors of mortality. In receiver operating characteristic curve analysis a cut...

  8. Vector synthesis high-resolution electrocardiography, atrial natriuretic peptide and N-terminal prohormone brain natriuretic peptide for estimation of cardiac load in pregnancy.

    Science.gov (United States)

    Tanaka, Shino; Oyama, Rie; Fukushima, Akimune; Kikuchi, Akihiko; Sugiyama, Toru

    2016-12-01

    We analyzed atrial natriuretic peptide (ANP), N-terminal pro-brain natriuretic natriuretic peptide (NT-proBNP) and vector synthesis high-resolution electrocardiography (ECG), to estimate cardiac load with circulatory dynamic change from pregnancy through the post-partum period. The subjects were singleton pregnant women (n = 19), who were divided into three stages: stage 1, 34-36 weeks of gestation; stage 2, 2-6 post-partum days; and stage 3, 1-3 months after delivery. Vector synthesis high-resolution ECG, ANP and NT-proBNP were analyzed for all subjects. A pregnant woman with massive uterin liomyoma expressed largest the corrected recover time (RTc) dispersion in I + II of tow Dimensional (2D) color distribution map ANP and NT-proBNP were significantly higher in stage 2 than in stages 1 and 3. ANP, NT-proBNP and vector synthesis high-resolution ECG there might be able to evaluate cardiac load of normal pregnancy. © 2016 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.

  9. Perioperative NT-proBNP level: Potential prognostic markers in children undergoing congenital heart disease surgery.

    Science.gov (United States)

    Qu, Jiangbo; Liang, Huiying; Zhou, Na; Li, Lijuan; Wang, Yanfei; Li, Jianbin; Cui, Yanqin

    2017-08-01

    To assess the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at different time points and early outcome, and to evaluate the reliability of NT-proBNP level as a predictor of early outcome after surgery in a large series of children with congenital heart disease (CHD). A retrospective observational study involving 363 consecutive children with CHD was used. Plasma NT-proBNP records were obtained for each patient before and 1, 12, and 36 hours after surgery. The specificity, sensitivity, and prediction value of NT-proBNP in predicting early postoperative outcomes were determined. Analyses confirmed that time-varying NT-proBNP level, particularly 1-hour postoperative levels, had prognostic value on the prediction of prolonged duration of mechanical ventilation, intensive care unit (ICU) stay, and inotropic therapy. Joint modeling analyses of a linear mixed effects model for NT-proBNP from before to 36 hours after surgery and generalized linear models for the duration of the mechanical ventilation, ICU stay, and inotropic therapy showed that a 1% increase in NT-proBNP was associated with 5.5%, 3.9%, and 3.5% relative increases in expected duration of mechanical ventilation, ICU stay, and inotropic therapy, respectively; related P values were .001, .001, and .01, respectively. After CHD surgery, the perioperative NT-proBNP levels might be powerful markers to identify subjects at higher risk for worse outcome. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  10. Echocardiographic evaluation and N-terminal pro-brain natriuretic peptide measurement of patients hospitalized for heart failure during weaning from mechanical ventilation.

    Science.gov (United States)

    Gerbaud, E; Erickson, M; Grenouillet-Delacre, M; Beauvieux, M-C; Coste, P; Durrieu-Jaïs, C; Hilbert, G; Castaing, Y; Vargas, F

    2012-04-01

    Weaning patients with heart failure who have required mechanical ventilation remains challenging. We evaluated echocardiographic indexes and N-terminal pro-brain natriuretic peptide (NT-proBNP) as markers of acute cardiac dysfunction before and after spontaneous breathing trials (SBT) in such patients to assess their ability to predict subsequent successful extubation. Forty-four patients who underwent their first SBT were prospectively included. Plasma levels of NT-proBNP and transthoracic echocardiography indices including cardiac index, E/A ratio and E/Ea ratio were recorded immediately before commencing and just before the end of SBT. Ten patients (22.7%) failed their SBT. No significant difference was observed concerning baseline echocardiographic data and NT-proBNP level between the patients who succeeded the SBT or those that failed. Cardiac index increased significantly at end-SBT in patients who passed (3.3 [3.06-3.77] vs. 3 [2.68-3.3] L/min/m(2), Pfailed. E/Ea ratio (16.8 [8.5-27.3] vs. 10.7 [6.7-20.5], P=0.006) and NT-proBNP level (8199 [3106-10949] vs. 4200 [1855-7125] pg/mL, P=0.004) increased significantly in those who failed the SBT, in contrast to the weaning success group where they remained unchanged. Neither NT-proBNP level nor the studied echocardiographic indices before SBT were able to predict SBT outcome in patients presenting with severe heart failure. Failure to increase the cardiac index and increases in both E/Ea ratio and NT-proBNP levels were seen at end-SBT in patients who failed the SBT, and may reflect failure of myocardial reserve to cope with the stress of SBT.

  11. N-terminal pro-B-type natriuretic peptide, left ventricular mass, and incident heart failure: Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Choi, Eui-Young; Bahrami, Hossein; Wu, Colin O; Greenland, Philip; Cushman, Mary; Daniels, Lori B; Almeida, Andre L C; Yoneyama, Kihei; Opdahl, Anders; Jain, Aditya; Criqui, Michael H; Siscovick, David; Darwin, Christine; Maisel, Alan; Bluemke, David A; Lima, Joao A C

    2012-11-01

    Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population. A total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54-2.46, P10% =0.175, P=0.019; category-less net reclassification index=0.561, P<0.001). Plasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

  12. Associations of N-terminal pro-B-type natriuretic peptide with kidney function decline in persons without clinical heart failure in the Heart and Soul Study.

    Science.gov (United States)

    Park, Meyeon; Vittinghoff, Eric; Shlipak, Michael G; Mishra, Rakesh; Whooley, Mary; Bansal, Nisha

    2014-12-01

    Subclinical volume overload in the absence of diagnosed heart failure (HF) may be an underrecognized contributor to kidney function decline in coronary artery disease (CAD) patients. We evaluated associations of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of ventricular stretch, with change in estimated glomerular filtration rate (eGFR). We evaluated 535 patients with stable CAD and no history of HF, who were enrolled in the Heart and Soul Study and followed for 5 years. N-terminal pro-B-type natriuretic peptide was measured at baseline. We evaluated the associations of NT-proBNP with change in kidney function over 5 years: (a) annual percent change in eGFR, (b) rapid kidney function loss (> 3% per year for 5 years), and (c) incident eGFR 280.9 pg/mL) had a greater odds of rapid kidney function loss after full adjustment (odds ratio 2.95; 95% CI 1-8.65; P = .0492). Associations with incident eGFR < 60 mL/min per 1.73 m2 were also significant (adjusted odds ratio 4.23; 95% CI 1.05-16.98; P = .0422). Results were similar when analyzed using BNP as the predictor. N-terminal pro-B-type natriuretic peptide and BNP are strongly and independently associated with accelerated kidney function loss, even in the absence of clinical HF. These findings suggest that subclinical cardiovascular dysfunction may contribute to elevated kidney disease risk in persons with CAD. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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.

  14. Regulation of Brown and White Adipocyte Transcriptome by the Transcriptional Coactivator NT-PGC-1α.

    Directory of Open Access Journals (Sweden)

    Jihyun Kim

    Full Text Available The β3-adrenergic receptor (AR signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β3-AR signaling highly induces the expression of transcriptional coactivator PGC-1α and its splice variant N-terminal (NT-PGC-1α, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of transcription factors. We previously reported that NT-PGC-1α is able to increase mitochondrial number and activity in cultured brown adipocytes by promoting the expression of mitochondrial and thermogenic genes. In the present study, we performed genome-wide profiling of NT-PGC-1α-responsive genes in brown adipocytes to identify genes potentially regulated by NT-PGC-1α. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, canonical pathway analysis of NT-PGC-1α-responsive genes identified several metabolic pathways including glycolysis and fatty acid synthesis. In order to validate the identified genes in vivo, we utilized the FL-PGC-1α-/- mouse that is deficient in full-length PGC-1α (FL-PGC-1α but expresses a slightly shorter and functionally equivalent form of NT-PGC-1α (NT-PGC-1α254. The β3-AR-induced increase of NT-PGC-1α254 in FL-PGC-1α-/- brown and white adipose tissue was closely associated with elevated expression of genes involved in thermogenesis, mitochondrial oxidative metabolism, glycolysis and fatty acid synthesis. Increased adipose tissue thermogenesis by β3-AR activation resulted in attenuation of adipose tissue expansion in FL-PGC-1α-/- adipose tissue under the high-fat diet condition. Together, the data strengthen our previous findings that NT-PGC-1

  15. Exercise induced laryngeal obstruction: a review of diagnosis and management.

    Science.gov (United States)

    Liyanagedera, Savinda; McLeod, Robert; Elhassan, Hassan A

    2017-04-01

    Exercise induced laryngeal obstruction (EILO) is a condition where inappropriate vocal cord or glottic closure occurs during exercise. This review of the literature provides an overview of the current understanding of the definition, epidemiology, diagnosis and management of EILO. Using The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines the Cochrane, Embase, Ovid MEDLINE and PubMed databases were searched. Four search domains "exercise", "induced", "laryngeal" and "obstruction" were used. Primary searching found 469 records, 308 were excluded following screening of titles and citation. 100 were duplicates, a further 47 studies were excluded after applying inclusion and exclusion criteria. Two studies were identified following cross-referencing. A total of 15 studies were included. The last search date was 6/06/15. Average prevalence in the general adolescent population and athletes was 7.1 and 35.2 %, respectively. Dyspnoea was reported in 96.5, 99 and 100 % of three EILO patient cohorts. Two studies (n = 107) reported continuous laryngoscopy during exercise (CLE) testing could differentiate between patients and controls. In two studies (n = 33) the visual analogue scale (VAS) showed a beneficial effect of endoscopic supraglottoplasty (ES). Thirty-eight out of 43 patients who received two or more laryngeal control therapy sessions (LCT) had improvement or resolution of EILO symptoms. Exercise induced dyspnoea is the most common EILO symptom. EILO has a high occurrence in adolescents and athletes. The CLE test is the current gold standard for EILO diagnostics. Management of EILO includes both surgical and non-surgical interventions.

  16. Management of exercise-induced bronchospasm in NCAA athletic programs

    Science.gov (United States)

    Parsons, Jonathan P.; Pestritto, Vincent; Phillips, Gary; Kaeding, Christopher; Best, Thomas M.; Wadley, Gail; Mastronarde, John G.

    2009-01-01

    Purpose The prevalence of exercise-induced bronchospasm (EIB) is significantly higher in athletes than the general population, and can result in significant morbidity in young, competitive athletes. Guidelines emphasize that education and written treatment protocols improve clinical outcomes for asthmatics. Evidence also supports objective testing when exercise-induced bronchospasm is suspected, immediate availability of rescue inhalers, and involvement of asthma specialists in the care of asthmatic athletes. We sought to determine how EIB is managed at National Collegiate Athletic Association (NCAA) sports medicine programs. Methods A survey consisting of multiple-choice questions related to exercise-induced bronchospasm in athletes was sent electronically to 3200 athletic trainers affiliated with NCAA sports medicine programs. Results 541 athletic trainers responded. A minority of athletic trainers surveyed (21%) indicated an asthma management protocol exists at their institution. 22% indicated that pulmonologists are on staff in or consultants to the sports medicine department. Many indicated a short-acting beta-agonist is not required to be available at all practices (39%) and games (41%) and few athletic trainers indicated their programs utilize objective testing to diagnose EIB (17%). Regression modeling demonstrated education about EIB and involvement of pulmonologists significantly improved adherence to current consensus guidelines. Conclusions Based on our data, many NCAA sports medicine programs do not manage athletes with EIB according to current consensus guidelines. This may result in inaccurate diagnoses and may be detrimental to clinical outcomes and the overall health of student athletes. Providing education about EIB and involvement of pulmonologists significantly increase adherence to guidelines which likely improves clinical care of athletes and potentially athletic performance. PMID:19276862

  17. Exercise-Induced Oxidative Stress Responses in the Pediatric Population

    Directory of Open Access Journals (Sweden)

    Alexandra Avloniti

    2017-01-01

    Full Text Available Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty.

  18. Relationship between N-terminal pro-B-type natriuretic peptide plasma levels and renal function evaluated with different formulae in older adult subjects admitted because of dyspnea.

    Science.gov (United States)

    Fabbian, Fabio; De Giorgi, Alfredo; Portaluppi, Francesco; Zuliani, Giovanni

    2012-01-01

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels are associated with congestive heart failure severity, and are an important diagnostic tool for assessing patients with acute dyspnea. Reduced renal function increases NT-proBNP concentrations, and therefore it might be a confounding factor in chronic kidney disease (CKD) patients. The aim of the present study was to relate NT-proBNP plasma levels to different stages of renal function assessed with different methods in older adult subjects admitted because of dyspnea. NT-proBNP plasma levels (Roche Diagnostic, Mannheim, Germany) were measured in 134 older adult patients (age: 80 ± 6 years) admitted to hospital because of dyspnea. Anthropometrics, anamnesis, and biochemical data were collected. Glomerular filtration rate (GFR) was evaluated with different equations, the 4 variables MDRD equations (GFR(MDRD186), GFR(MDRD175)), Mayo Clinic Quadratic formula (GFR(MAYO)), and the new CKD-EPI formula (GFR(CKD-EPI)). Patients were classified into the five K/DOQI stages of CKD and median NT-proBNP values were calculated evaluating their relationship with GFR. Median NT-proBNP values were better stratified into the five K/DOQI stages by GFR(MAYO) (stage 1 (n = 10) 1,640 pg/ml vs. stage 2 (n = 61) 2,371 pg/ml vs. stage 3 (n = 42) 3,815 pg/ml vs. stage 4 (n = 18) 6,320 pg/ml vs. stage 5 (n = 3) 7,256 pg/ml, p = 0.017). However, similar results were obtained with the other formulae. NT-proBNP was negatively correlated with GFR as evaluated with all the different formulae (r -0.25 to -0.29; all p formula appears to better stratify NT-proBNP in older adult subjects. Renal function should be considered when interpreting NT-proBNP levels in older adult patients admitted for dyspnoea. Copyright © 2011 S. Karger AG, Basel.

  19. Relationship between N-terminal pro-brain natriuretic peptide, obesity and the risk of heart failure in middle-aged German adults.

    Directory of Open Access Journals (Sweden)

    Janine Wirth

    Full Text Available Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status.A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years and heart failure cases outside the sub-cohort (n = 197. Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2.Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR and 95% confidence interval (CI: 2.56 (1.49-4.41 for the top versus bottom tertile of NT-proBNP, ptrend:<0.01. In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85-3.49, 2.72 (1.42-5.22, and for obese: 3.29 (1.04-10.40, reference, 3.74 (1.52-9.21.Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms.

  20. Vitamin C for asthma and exercise-induced bronchoconstriction.

    Science.gov (United States)

    Milan, Stephen J; Hart, Anna; Wilkinson, Mark

    2013-10-23

    Dietary antioxidants, such as vitamin C, in the epithelial lining and lining fluids of the lung may be beneficial in the reduction of oxidative damage (Arab 2002). They may therefore be of benefit in reducing symptoms of inflammatory airway conditions such as asthma, and may also be beneficial in reducing exercise-induced bronchoconstriction, which is a well-recognised feature of asthma and is considered a marker of airways inflammation. However, the association between dietary antioxidants and asthma severity or exercise-induced bronchoconstriction is not fully understood. To examine the effects of vitamin C supplementation on exacerbations and health-related quality of life (HRQL) in adults and children with asthma or exercise-induced bronchoconstriction compared to placebo or no vitamin C. We identified trials from the Cochrane Airways Group's Specialised Register (CAGR). The Register contains trial reports identified through systematic searches of a number of bibliographic databases, and handsearching of journals and meeting abstracts. We also searched trial registry websites. The searches were conducted in December 2012. We included randomised controlled trials (RCTs). We included both adults and children with a diagnosis of asthma. In separate analyses we considered trials with a diagnosis of exercise-induced bronchoconstriction (or exercise-induced asthma). We included trials comparing vitamin C supplementation with placebo, or vitamin C supplementation with no supplementation. We included trials where the asthma management of both treatment and control groups provided similar background therapy. The primary focus of the review is on daily vitamin C supplementation to prevent exacerbations and improve HRQL. The short-term use of vitamin C at the time of exacerbations or for cold symptoms in people with asthma are outside the scope of this review. Two review authors independently screened the titles and abstracts of potential studies, and subsequently

  1. Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Nielsen, Per H

    2006-01-01

    BACKGROUND: The usefulness of brain-natriuretic-peptide (BNP) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) for monitoring of chronic heart failure (CHF) patients has been questioned because of high levels of unexplained variation. AIMS: Week-to-week total variance (CV(T)), unexplained...... plasma concentrations of BNP and NT-proBNP, clinical and laboratory variables in 20 CHF patients with a 7-days interval. Only patients considered to be in steady state were included. The CV(I) was 15% (BNP) and 8% (NT-proBNP). CV(T) was 16% (BNP) and 8% (NT-proBNP) and RCV was 43% (BNP) and 23% (NT...

  2. Relationship between CCR and NT-proBNP in Chinese HF patients, and their correlations with severity of HF.

    Science.gov (United States)

    Lu, Zhigang; Wang, Bo; Wang, Yunliang; Qian, Xueqing; Zheng, Wei; Wei, Meng

    2014-01-01

    To evaluate the relationship between creatinine clearance rate (CCR) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients and their correlations with HF severity. Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. The following variables were compared among these three groups: age, sex, body mass index (BMI), smoking status, hypertension, diabetes, NT-proBNP, creatinine (Cr), uric acid (UA), left ventricular end-diastolic diameter (LVEDD), and CCR. The biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR varied significantly in the three groups, and these variables were positively correlated with the NHYA classification. The levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for HF. At the same time, there was a significant negative correlation between the levels of NT-proBNP and CCR. The area under the receiver operating characteristic curve suggested that the NT-proBNP and CCR have high accuracy for diagnosis of HF and have clinical diagnostic value. NT-proBNP and CCR may be important biomarkers in evaluating the severity of HF.

  3. Use of post-exercise laryngoscopy to evaluate exercise induced dyspnea.

    LENUS (Irish Health Repository)

    McNally, P

    2010-10-01

    We present the case of a child with asthma who continued to have marked exercise induced dyspnea despite appropriate treatment, and in the face of adequate control of all other asthma symptoms. Spirometry showed a marked truncation of inspiratory flow, and laryngoscopy performed immediately after exercise showed laryngomalacia with dynamic, partial inspiratory obstruction. Exercise induced laryngomalacia (EIL) is a rare cause of exercise induced dyspnea which is diagnosed by post exercise flexible laryngoscopy and may require supraglottoplasty.

  4. Laser acupuncture in children and adolescents with exercise induced asthma.

    Science.gov (United States)

    Gruber, W; Eber, E; Malle-Scheid, D; Pfleger, A; Weinhandl, E; Dorfer, L; Zach, M S

    2002-03-01

    Laser acupuncture, a painless technique, is a widely used alternative treatment method for childhood asthma, although its efficacy has not been proved in controlled clinical studies. A double blind, placebo controlled, crossover study was performed to investigate the possible protective effect of a single laser acupuncture treatment on cold dry air hyperventilation induced bronchoconstriction in 44 children and adolescents of mean age 11.9 years (range 7.5-16.7) with exercise induced asthma. Laser acupuncture was performed on real and placebo points in random order on two consecutive days. Lung function was measured before laser acupuncture, immediately after laser acupuncture (just before cold dry air challenge (CACh)), and 3 and 15 minutes after CACh. CACh consisted of a 4 minute isocapnic hyperventilation of -10 degrees C absolute dry air. Comparison of real acupuncture with placebo acupuncture showed no significant differences in the mean maximum CACh induced decrease in forced expiratory volume in 1 second (27.2 (18.2)% v 23.8 (16.2)%) and maximal expiratory flow at 25% remaining vital capacity (51.6 (20.8)% v 44.4 (22.3)%). A single laser acupuncture treatment offers no protection against exercise induced bronchoconstriction in paediatric and adolescent patients.

  5. N-terminal nesprin-2 variants regulate β-catenin signalling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qiuping; Minaisah, Rose-Marie; Ferraro, Elisa; Li, Chen; Porter, Lauren J.; Zhou, Can; Gao, Fang; Zhang, Junyi; Rajgor, Dipen; Autore, Flavia; Shanahan, Catherine M.; Warren, Derek T., E-mail: derek.warren@kcl.ac.uk

    2016-07-15

    The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragment of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity. - Highlights: • N-terminal nesprin-2 variants display cell specific expression patterns. • N-terminal spectrin repeats of nesprin-2 interact with β-catenin. • N-terminal nesprin-2 variants scaffold β-catenin at cell-cell junctions.. • Nesprin-2 variants play multiple roles in β-catenin signalling.

  6. N-terminal nesprin-2 variants regulate β-catenin signalling

    International Nuclear Information System (INIS)

    Zhang, Qiuping; Minaisah, Rose-Marie; Ferraro, Elisa; Li, Chen; Porter, Lauren J.; Zhou, Can; Gao, Fang; Zhang, Junyi; Rajgor, Dipen; Autore, Flavia; Shanahan, Catherine M.; Warren, Derek T.

    2016-01-01

    The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragment of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity. - Highlights: • N-terminal nesprin-2 variants display cell specific expression patterns. • N-terminal spectrin repeats of nesprin-2 interact with β-catenin. • N-terminal nesprin-2 variants scaffold β-catenin at cell-cell junctions.. • Nesprin-2 variants play multiple roles in β-catenin signalling.

  7. [N-terminal pro-B-type natriuretic peptide value for prediction of mortality among critically ill patients in different age groups in intensive care unit].

    Science.gov (United States)

    Li, Hailing; Wang, Hongping; Lou, Yunpeng; Miao, Wenli; Sha, Ning

    2014-07-01

    To investigate N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoff value for the mortality in different age groups in critically ill patients. A retrospective study was conducted. 295 patients admitted to the intensive care unit (ICU) of 401st Hospital of PLA from January 2011 to October 2012 were divided into two groups according to age [group with agepredicting the mortality. (1) There were no significant differences in the length of stay in ICU, mechanical ventilation rate, the mortality, the incidence of cardiovascular disease, digestive disease, neurologic disease, and the number of patients having received operation, HCT, PCT and CRP between the two groups (all P>0.05). The percentage of the male, the APACHEII score, the percentage of respiratory disease, and NT-proBNP in group with age≥65 years old were higher than those of the group with agepredictive value (90.0% vs. 75.8%), and negative predictive value (62.2% vs. 53.8%) with cutoff value of NT-proBNP (2 882 ng/L) in group with ageprediction of mortality in the critically ill patients maybe more objective and accurate.

  8. Exercise-induced bronchospasm: coding and billing for physician services.

    Science.gov (United States)

    Pohlig, Carol

    2009-01-01

    Physician reporting of the service to insurance companies for reimbursement is multifaceted and perplexing to those who do not understand the factors to consider. Test selection should be individualized based on the patient's history and/or needs. Federal regulations concerning physician supervision of diagnostic tests mandate different levels of physician supervision based on the type and complexity of the test. Many factors play a key role in physician claim submission. These include testing location, component services, coding edits, and additional visits. Medical necessity of the service(s) must also be demonstrated for payer consideration and reimbursement. The following article reviews various tests for exercise-induced bronchospasm and focuses on issues to assist the physician in reporting the services accurately and appropriately.

  9. Supraglottoplasty as treatment of exercise induced laryngeal obstruction (EILO)

    DEFF Research Database (Denmark)

    Mehlum, Camilla Slot; Walsted, Emil Schwarz; Godballe, Christian

    2016-01-01

    Breathing difficulties during exertion may be caused by exercise-induced laryngeal obstruction (EILO). The diagnosis depends on visualization of the larynx during exercise, i.e. by continuous laryngoscopic exercise (CLE) test. In case of severe supraglottic collapse and pronounced symptoms during...... or on very few patients. This study is the second larger-scale study that documents the positive effect of supraglottoplasty as treatment of EILO in terms of reduced respiratory symptoms and decreased laryngeal obstruction assessed by post-operative CLE test. We suggest that surgery is a well...... strenuous exertion, surgical treatment (supraglottoplasty) has been suggested. The aims of this study were to evaluate outcome and patient satisfaction after supraglottoplasty for EILO and to compare our results with previously reported data. During the period December 2010 to October 2013, 17 patients...

  10. Strenuous Exercise Induced Syncope Due to Coronary Artery Anomaly

    Directory of Open Access Journals (Sweden)

    Veysel Yavuz

    2014-09-01

    Full Text Available Coronary artery anomalies are among the neglected topics in cardiology. Anomalous origin of the left main coronary artery from the right sinus of valsalva is a rare coronary anomaly observed in 0.15% of patients. During exercise, the distended aorta and pulmonary artery with increased blood flow may squeeze the Left Main Coronary Artery (LMCA between them. Even though arrhythmias are common causes of syncope, one should also think about aberrant coronary artery in the patients with syncope of unexplained origin. Patients experiencing exercise induced syncope accompanied by symptoms of coronary ischemia (typically: chest pain, ischemic findings on ECG, and raised cardiac markers should be referred to diagnostic coronary angiography.

  11. Exercise-induced metallothionein expression in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Pernille; Keller, Charlotte

    2005-01-01

    in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

  12. Antral content, secretion and peripheral metabolism of N-terminal progastrin fragments

    DEFF Research Database (Denmark)

    Goetze, Jens Peter; Hansen, Carsten Palnaes; Rehfeld, Jens F

    2006-01-01

    OBJECTIVES: In addition to the acid-stimulatory gastrins, progastrin also release N-terminal fragments. In order to examine the cellular content, secretion and peripheral metabolism of these fragments, we developed an immunoassay specific for the N-terminal sequence of human progastrin. RESULTS......-terminal progastrin fragments. The basal concentration of N-terminal fragments in normal human plasma was almost 30-fold higher than that of the amidated, acid-stimulatory gastrins (286 pmol/l versus 9.8 pmol/l, n=26, P...-35 in circulation was 30 min, and a pig model revealed the kidneys and the vasculature to the head as the primary sites of degradation. CONCLUSION: The cellular and circulatory concentration profiles of N-terminal progastrin fragments differ markedly from those of the acid-stimulatory gastrins. The high basal...

  13. BNP and N-terminal proBNP are both extracted in the normal kidney

    DEFF Research Database (Denmark)

    Goetze, J P; Jensen, G; Møller, S

    2006-01-01

    BACKGROUND: Increased plasma concentrations of cardiac-derived B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We...... with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N-terminal proBNP and BNP. RESULTS: Neither the peripheral N-terminal proBNP (13, 11, 19 pmol L(-1), NS) nor the BNP plasma concentrations (4, 12, 9...... compared with BNP (0.00 vs. 0.125, P = 0.007). CONCLUSIONS: A comparable renal elimination of N-terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may...

  14. BNP and N-terminal proBNP are both extracted in the normal kidney

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Jensen, Gorm Boje; Møller, Søren

    2006-01-01

    Background Increased plasma concentrations of cardiac-derived B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We...... with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N-terminal proBNP and BNP. Results Neither the peripheral N-terminal proBNP (13, 11, 19 pmol L(-1), NS) nor the BNP plasma concentrations (4, 12, 9...... compared with BNP (0.00 vs. 0.125, P = 0.007). Conclusions A comparable renal elimination of N-terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may...

  15. Familial Paroxysmal Exercise-Induced Dystonia: Atypical Presentation of Autosomal Dominant GTP-Cyclohydrolase 1 Deficiency

    Science.gov (United States)

    Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

    2010-01-01

    Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…

  16. Prolonged recovery from exercise-induced asthma with increasing age in childhood

    NARCIS (Netherlands)

    Hofstra, W. B.; Sterk, P. J.; Neijens, H. J.; Kouwenberg, J. M.; Duiverman, E. J.

    1995-01-01

    It has been suggested that children with asthma recover more quickly from exercise-induced bronchoconstriction than adults. On the basis of clinical observation we hypothesized that recovery rate from exercise-induced asthma (EIA) in childhood also decreases with age. In 14 children (aged 7-12

  17. Comparison between two assessment methods for exercise-induced laryngeal obstructions

    DEFF Research Database (Denmark)

    Norlander, Katarina; Christensen, Pernille Meyer; Maat, Robert C.

    2016-01-01

    Exercise-induced laryngeal obstructions (E-ILOs) are important differential diagnoses to exercise-induced asthma and are diagnosed by the continuous laryngoscopy exercise (CLE) test. There are two different methods for evaluating the severity of E-ILOs using recordings from the CLE test; the CLE...

  18. The biological variation of N-terminal pro-brain natriuretic peptide in postmenopausal women with type 2 diabetes: a case control study.

    Science.gov (United States)

    González, Susana; Kilpatrick, Eric S; Atkin, Stephen L

    2012-01-01

    The incidence of heart failure in type 2 diabetes is high and it has poorer prognosis when compared with patients without diabetes. Access to echocardiography is limited and alternative methods to identify early heart failure such as the measurement of natriuretic peptides levels have been proposed. However, their wide biological variation could limit their clinical utility. Our aim was to determine if the intrinsic biological variation of one of these peptides, N-terminal proBNP, is as wide in type 2 diabetes as it is in health and to calculate the critical difference values that could be utilised in clinical practice to ensure changes observed between two samples are due to intervention rather than to its biological variability. 12 postmenopausal women with diet controlled type 2 diabetes and without heart failure were compared with 11 control postmenopausal women without diabetes. N-terminal proBNP levels were measured on 10 occasions. The biological variation was calculated according to Fraser's methods. The mean NT-proBNP level was similar in both groups (mean ± standard deviation; type 2 diabetes, 10.7 pmol/L± 8.5 versus 8.49±6.0 pmol/L, p = 0.42). The biological variation was also similarly wide. The critical difference in patients with type 2 diabetes was between -70% and ±236%. Type 2 diabetes does not appear to significantly influence the marked biological variation of N-terminal proBNP in postmenopausal women. The critical difference values reported in this study could be used to titrate therapy or monitor response to interventions although the change required in between samples is wide and this might limit its utility.

  19. The biological variation of N-terminal pro-brain natriuretic peptide in postmenopausal women with type 2 diabetes: a case control study.

    Directory of Open Access Journals (Sweden)

    Susana González

    Full Text Available BACKGROUND: The incidence of heart failure in type 2 diabetes is high and it has poorer prognosis when compared with patients without diabetes. Access to echocardiography is limited and alternative methods to identify early heart failure such as the measurement of natriuretic peptides levels have been proposed. However, their wide biological variation could limit their clinical utility. Our aim was to determine if the intrinsic biological variation of one of these peptides, N-terminal proBNP, is as wide in type 2 diabetes as it is in health and to calculate the critical difference values that could be utilised in clinical practice to ensure changes observed between two samples are due to intervention rather than to its biological variability. METHODOLOGY/PRINCIPAL FINDINGS: 12 postmenopausal women with diet controlled type 2 diabetes and without heart failure were compared with 11 control postmenopausal women without diabetes. N-terminal proBNP levels were measured on 10 occasions. The biological variation was calculated according to Fraser's methods. The mean NT-proBNP level was similar in both groups (mean ± standard deviation; type 2 diabetes, 10.7 pmol/L± 8.5 versus 8.49±6.0 pmol/L, p = 0.42. The biological variation was also similarly wide. The critical difference in patients with type 2 diabetes was between -70% and ±236%. CONCLUSIONS: Type 2 diabetes does not appear to significantly influence the marked biological variation of N-terminal proBNP in postmenopausal women. The critical difference values reported in this study could be used to titrate therapy or monitor response to interventions although the change required in between samples is wide and this might limit its utility.

  20. N-terminal Proteomics Assisted Profiling of the Unexplored Translation Initiation Landscape in Arabidopsis thaliana.

    Science.gov (United States)

    Willems, Patrick; Ndah, Elvis; Jonckheere, Veronique; Stael, Simon; Sticker, Adriaan; Martens, Lennart; Van Breusegem, Frank; Gevaert, Kris; Van Damme, Petra

    2017-06-01

    Proteogenomics is an emerging research field yet lacking a uniform method of analysis. Proteogenomic studies in which N-terminal proteomics and ribosome profiling are combined, suggest that a high number of protein start sites are currently missing in genome annotations. We constructed a proteogenomic pipeline specific for the analysis of N-terminal proteomics data, with the aim of discovering novel translational start sites outside annotated protein coding regions. In summary, unidentified MS/MS spectra were matched to a specific N-terminal peptide library encompassing protein N termini encoded in the Arabidopsis thaliana genome. After a stringent false discovery rate filtering, 117 protein N termini compliant with N-terminal methionine excision specificity and indicative of translation initiation were found. These include N-terminal protein extensions and translation from transposable elements and pseudogenes. Gene prediction provided supporting protein-coding models for approximately half of the protein N termini. Besides the prediction of functional domains (partially) contained within the newly predicted ORFs, further supporting evidence of translation was found in the recently released Araport11 genome re-annotation of Arabidopsis and computational translations of sequences stored in public repositories. Most interestingly, complementary evidence by ribosome profiling was found for 23 protein N termini. Finally, by analyzing protein N-terminal peptides, an in silico analysis demonstrates the applicability of our N-terminal proteogenomics strategy in revealing protein-coding potential in species with well- and poorly-annotated genomes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Sandra Goetze

    2009-11-01

    Full Text Available Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (XPX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (XPX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species.

  2. 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.

  3. Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

    Science.gov (United States)

    Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

    2008-03-01

    Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes exercising as well as 2 days later, 21 age-matched male patients classified as stage-B according to ACC/AHA guidelines and 35 healthy age-matched males, we evaluated NT-proBNP and 3rd generation's cTnT by electrochemiluminescence immunoassay. All participants underwent a detailed cardiac protocol including echocardiography and electrocardiogram (ECG). In athletes, cTnT consistently remained exercising as well as after 2 days. NTproBNP immediately after exercising was 58.27+/-19.48 ng/L, without reaching pathological levels, decreasing 2 days later to 22.93+/-10.22 ng/L. Our patients maintained high levels of NTproBNP, as much as a six-fold increase with reference to the levels of our study's control group and with cTnT exercising. NT-proBNP as a biological marker can reliably discriminate pathological from physiological cardiac hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

  4. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction

    Directory of Open Access Journals (Sweden)

    Adrish M

    2017-04-01

    Full Text Available Muhammad Adrish,1 Varalaxmi Bhavani Nannaka,2 Edison J Cano,3 Bharat Bajantri,1 Gilda Diaz-Fuentes1 1Division of Pulmonary and Critical Care Medicine, Bronx-Lebanon Hospital Center, Icahn School of Medicine at Mount Sinai, 2Department of Critical Care Medicine, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, 3Department of Medicine, Bronx-Lebanon Hospital Center, Icahn School of Medicine at Mount Sinai, Bronx, NY, USA Background: B-type natriuretic peptide (BNP and the N-terminal fragment of pro-BNP (NT-pro-BNP are established biomarkers of heart failure. Increased levels of natriuretic peptide (NP have been associated with poor outcomes in acute exacerbation of COPD (AECOPD; however, most studies did not address the conditions that can also increase NT-pro-BNP levels. We aimed to determine if NT-pro-BNP levels correlate with outcomes of AECOPD in patients without heart failure and other conditions that can affect NT-pro-BNP levels.Methods: We conducted a retrospective study in patients hospitalized for AECOPD with available NT-pro-BNP levels and normal left ventricular ejection fraction. We compared patients with normal and elevated NT-pro-BNP levels and analyzed the clinical and outcome data.Results: A total of 167 of 1,420 (11.7% patients met the study criteria. A total of 77% of male patients and 53% of female patients had elevated NT-pro-BNP levels (P=0.0031. NT-pro-BNP levels were not associated with COPD severity and comorbid illnesses. Log-transformed NT-pro-BNP levels were positively associated with echocardiographically estimated right ventricular systolic pressure (r=0.3658; 95% confidence interval [CI]: 0.2060–0.5067; P<0.0001. Patients with elevated NT-pro-BNP levels were more likely to require intensive care (63% vs 43%; P=0.0207 and had a longer hospital length of stay (P=0.0052. There were no differences in the need for noninvasive positive pressure ventilation (P=0.1245 or mechanical

  5. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).

    Science.gov (United States)

    Hijazi, Ziad; Wallentin, Lars; Siegbahn, Agneta; Andersson, Ulrika; Christersson, Christina; Ezekowitz, Justin; Gersh, Bernard J; Hanna, Michael; Hohnloser, Stefan; Horowitz, John; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Granger, Christopher B

    2013-06-04

    This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p ARISTOTLE]; NCT00412984). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  6. N-terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects

    Science.gov (United States)

    Varland, Sylvia; Osberg, Camilla; Arnesen, Thomas

    2015-01-01

    The vast majority of eukaryotic proteins are N-terminally modified by one or more processing enzymes. Enzymes acting on the very first amino acid of a polypeptide include different peptidases, transferases, and ligases. Methionine aminopeptidases excise the initiator methionine leaving the nascent polypeptide with a newly exposed amino acid that may be further modified. N-terminal acetyl-, methyl-, myristoyl-, and palmitoyltransferases may attach an acetyl, methyl, myristoyl, or palmitoyl group, respectively, to the α-amino group of the target protein N-terminus. With the action of ubiquitin ligases, one or several ubiquitin molecules are transferred, and hence, constitute the N-terminal modification. Modifications at protein N-termini represent an important contribution to proteomic diversity and complexity, and are essential for protein regulation and cellular signaling. Consequently, dysregulation of the N-terminal modifying enzymes is implicated in human diseases. We here review the different protein N-terminal modifications occurring co- or post-translationally with emphasis on the responsible enzymes and their substrate specificities. PMID:25914051

  7. Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Daniel C.; Hammill, Jared T.; Min, Jaeki; Rhee, David Y.; Connelly, Michele; Sviderskiy, Vladislav O.; Bhasin, Deepak; Chen, Yizhe; Ong, Su-Sien; Chai, Sergio C.; Goktug, Asli N.; Huang, Guochang; Monda, Julie K.; Low, Jonathan; Kim, Ho Shin; Paulo, Joao A.; Cannon, Joe R.; Shelat, Anang A.; Chen, Taosheng; Kelsall, Ian R.; Alpi, Arno F.; Pagala, Vishwajeeth; Wang, Xusheng; Peng, Junmin; Singh , Bhuvanesh; Harper, J. Wade; Schulman, Brenda A.; Guy, R. Kip (MSKCC); (Dundee); (SJCH); (Harvard-Med); (MXPL)

    2017-06-05

    N-terminal acetylation is an abundant modification influencing protein functions. Because ~80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation–dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are highly selective with respect to other protein acetyl-amide–binding sites, inhibit NEDD8 ligation in vitro and in cells, and suppress anchorage-independent growth of a cell line with DCN1 amplification. Overall, our data demonstrate that N-terminal acetyl-dependent protein interactions are druggable targets and provide insights into targeting multiprotein E2–E3 ligases.

  8. N-terminal pro-brain natriuretic peptide for additional risk stratification in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy.

    Science.gov (United States)

    Windhausen, Fons; Hirsch, Alexander; Sanders, Gerard T; Cornel, Jan Hein; Fischer, Johan; van Straalen, Jan P; Tijssen, Jan G P; Verheugt, Freek W A; de Winter, Robbert J

    2007-04-01

    New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this study was to assess the association between baseline NT-proBNP levels and outcome in patients who have nSTE-ACS with an elevated cTnT and to determine whether patients with elevated NT-proBNP levels benefit from an early invasive treatment strategy. Baseline samples for NT-proBNP measurements were available in 1141 patients who have nSTE-ACS with an elevated cTnT randomized to an early or a selective invasive strategy. Patients were followed-up for the occurrence of death, myocardial infarction (MI), and rehospitalization for angina. We showed that increased levels of NT-proBNP were associated with several indicators of risk and severe coronary artery disease. Mortality by 1 year was 7.3% in the highest quartile (> or = 1170 ng/L for men, > or = 2150 ng/L for women) compared with 1.1% of patients in the lower 3 quartiles (P < .0001). N-terminal pro-brain natriuretic peptide (highest quartile vs lower 3 quartiles) was a strong independent predictor of mortality (hazard ratio 5.0, 95% CI 2.1-11.6, P = .0002). However, NT-proBNP levels were not associated with the incidence of recurrent MI by 1 year. Furthermore, we could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy in patients with an elevated NT-proBNP level. We confirmed that NT-proBNP is a strong independent predictor of mortality by 1 year but not of recurrent MI in patients who have nSTE-ACS with an elevated cTnT. We could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy.

  9. Exercise-induced bronchospasm in children: effects of asthma severity.

    Science.gov (United States)

    Cabral, A L; Conceição, G M; Fonseca-Guedes, C H; Martins, M A

    1999-06-01

    The prevalence of exercise-induced bronchospasm (EIB) in asthmatic individuals has been reported to vary from 40% to 90%. There are, however, few studies addressing the effects of asthma severity on airway responsiveness to exercise. The purpose of the present study was to investigate the effects of asthma severity on EIB in children. We studied 164 children classified as having intermittent (n = 63), mild persistent (n = 30), moderate persistent (n = 40), and severe persistent asthma (n = 31) according to the Global Initiative for Asthma classification. Subjects exercised for 6 min on a cycle ergometer at 80% of their maximum heart rate, and spirometry was performed before and 5, 10, and 20 min after exercise challenge. The prevalence of EIB in children with moderate or severe persistent asthma was significantly greater than in children with intermittent asthma (p children with intermittent asthma exhibited smaller changes in FEV1 than children in the other three groups (p children with more severe asthma, and that the intensity of response to exercise is not consistently related to the clinical severity of asthma.

  10. EXERCISE-INDUCED ASTHMA: FRESH INSIGHTS AND AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    KHAJOTIA R

    2008-01-01

    Full Text Available Exercise-induced asthma (EIA is a common condition affecting 12-15% of the population. Ninety percent of asthmatic individuals and 35-45% of patients with allergic rhinitis are afflicted by EIA, while 3-10% of the general population is also believed to suffer from this condition. EIA is a condition which is more prevalent in strenuous outdoor, cold weather and winter sports. The pathophysiology of EIA continues to intrigue medical physiologists. However, the water-loss hypothesis and the post-exertional airway-rewarming hypothesis are as yet the best accepted theories. EIA is best diagnosed by a good medical history and a free-run challenge test. A post-exertion decrease by 15% in FEV1 and PEFR is diagnostic of EIA. Sensitivity of exercise testing ranges from 55% to 80% while specificity is as high as 93%. EIA is a disorder that can be successfully treated by combining both non-pharmacological and pharmacological treatment options. Prompt diagnosis and treatment of this condition is vital if we hope to provide our patients with better overall health, better social life and a better self-image.

  11. Exercise-Induced Pulmonary Edema in a Triathlon

    Directory of Open Access Journals (Sweden)

    Hirotomo Yamanashi

    2015-01-01

    Full Text Available Introduction. Family physicians have more opportunities to attend athletic competitions as medical staff at first-aid centers because of the increasing popularity of endurance sports. Case. A 38-year-old man who participated in a triathlon race experienced difficulty in breathing after swimming and was moved to a first-aid center. His initial oxygen saturation was 82% and a thoracic computed tomography scan showed bilateral ground glass opacity in the peripheral lungs. His diagnosis was noncardiogenic pulmonary edema associated with exercise or swimming: exercise-induced pulmonary edema (EIPE or swimming-induced pulmonary edema (SIPE. Treatment with furosemide and corticosteroid relieved his symptoms of pulmonary edema. Discussion. Noncardiogenic pulmonary edema associated with endurance sports is not common, but knowledge about EIPE/SIPE or neurogenic pulmonary edema associated with hyponatremia, which is called Ayus-Arieff syndrome, is crucial. Knowledge and caution for possible risk factors, such as exposure to cold water or overhydration, are essential for both medical staff and endurance athletes. Conclusion. To determine the presence of pulmonary edema associated with strenuous exercise, oxygen saturation should be used as a screening tool at a first-aid center. To avoid risks for EIPE/SIPE, knowledge about these diseases is essential for medical staff and for athletes who perform extreme exercise.

  12. [Exercise-induced urticaria and angioedema - case report].

    Science.gov (United States)

    Stelmach, Iwona; Sztafińska, Anna; Lechańka, Joanna; Balcerak, Joanna; Jerzyńska, Joanna

    2014-01-01

    Urticaria is a heterogeneous group of disorders, with various clinical manifestations and intensity of symptoms. Urticaria can be induced with a wide variety of environmental stimuli, such as cold, pressure, vibration, sunlight, exercise, temperature changes, heat, and water. In a select group of patients, exercise can induce a spectrum of urticaria symptoms, ranging from cutaneous pruritus and warmth, generalised urticaria, angioedema, and the appearance of such additional manifestations as collapse, upper respiratory distress, and anaphylaxis. Specific provocation tests should be carried out on an individual basis to investigate the suspected cause and proper diagnosis. Modification of activities and behaviour is the mainstay of treatment in patients with physical urticaria. The aim of this study was to emphasise that primary care paediatricians should be able to recognise physical urticaria, supply a patient with rescue medications, and refer him/her to a specialist. In the article, the authors present a 13-year-old girl with typical urticaria lesions and angioedema after exercise. According to the history, physical examination, and provocation test, exercise-induced urticaria and angioedema were diagnosed.

  13. Diaphragmatic Breathing Reduces Exercise-Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Daniele Martarelli

    2011-01-01

    Full Text Available Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1 h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals.

  14. Exercise-induced effects on a gym atmosphere.

    Science.gov (United States)

    Žitnik, M; Bučar, K; Hiti, B; Barba, Ž; Rupnik, Z; Založnik, A; Žitnik, E; Rodrìguez, L; Mihevc, I; Žibert, J

    2016-06-01

    We report results of analysis of a month-long measurement of indoor air and environment quality parameters in one gym during sporting activities such as football, basketball, volleyball, badminton, boxing, and fitness. We have determined an average single person's contribution to the increase of temperature, humidity, and dust concentration in the gym air volume of 12500 m(3) : during 90-min exercise performed at an average heart rate of 143 ± 10 bpm, a single person evaporated 0.94 kg of water into the air by sweating, contributed 0.03 K to the air temperature rise and added 1.5 μg/m(3) and 5 ng/m(3) to the indoor concentration of inhalable particles (PM10 ) and Ca concentration, respectively. As the breathing at the observed exercise intensity was about three times faster with respect to the resting condition and as the exercise-induced PM10 concentration was about two times larger than outdoors, a sportsman in the gym would receive about a sixfold higher dose of PM10 inside than he/she would have received at rest outside. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Exercise-Induced Fatigue Impairs Bidirectional Corticostriatal Synaptic Plasticity.

    Science.gov (United States)

    Ma, Jing; Chen, Huimin; Liu, Xiaoli; Zhang, Lingtao; Qiao, Decai

    2018-01-01

    Exercise-induced fatigue (EF) is a ubiquitous phenomenon in sports competition and training. It can impair athletes' motor skill execution and cognition. Corticostriatal synaptic plasticity is considered to be the cellular mechanism of movement control and motor learning. However, the effect of EF on corticostriatal synaptic plasticity remains elusive. In the present study, using field excitatory postsynaptic potential recording, we found that the corticostriatal long-term potentiation (LTP) and long-term depression (LTD) were both impaired in EF mice. To further investigate the cellular mechanisms underlying the impaired synaptic plasticity in corticostriatal pathway, whole-cell patch clamp recordings were carried out on striatal medium spiny neurons (MSNs). MSNs in EF mice exhibited increased spontaneous excitatory postsynaptic current (sEPSC) frequency and decreased paired-pulse ratio (PPR), while with normal basic electrophysiological properties and normal sEPSC amplitude. Furthermore, the N-methyl-D-aspartate (NMDA)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) ratio of MSNs was reduced in EF mice. These results suggest that the enhanced presynaptic glutamate (Glu) release and downregulated postsynaptic NMDA receptor function lead to the impaired corticostriatal plasticity in EF mice. Taken together, our findings for the first time show that the bidirectional corticostriatal synaptic plasticity is impaired after EF, and suggest that the aberrant corticostriatal synaptic plasticity may be involved in the production and/or maintenance of EF.

  16. Speech-Language Pathology as a Primary Treatment for Exercise-Induced Laryngeal Obstruction.

    Science.gov (United States)

    Shaffer, Monica; Litts, Juliana K; Nauman, Emily; Haines, Jemma

    2018-05-01

    Exercise-induced laryngeal obstruction is a condition that restricts respiration during exercise via inappropriate glottic or supraglottic obstruction. The literature supports behavioral treatment provided by a speech-language pathologist as an effective means of treating exercise-induced laryngeal obstruction. Treatment includes educating the patient, training on relaxation, instruction on paced exercise, and use of various breathing techniques to optimize laryngeal aperture. Intervention for patients with exercise-induced laryngeal obstruction may be delivered by a speech-language pathologist, given their clinical skill of facilitating long-term behavioral change and expertise in the laryngeal mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Incremental value of a combination of cardiac troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein for prediction of mortality in end-stage renal disease

    DEFF Research Database (Denmark)

    Hallén, Jonas; Madsen, Lene Helleskov; Ladefoged, Søren

    2011-01-01

    Abstract Objective. To determine the relative prognostic merits of C-reactive protein (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for prediction of all-cause death in patients with end-stage renal disease (ESRD) receiving haemodialysis. Material...... and methods. This prospective, controlled cohort study included 109 patients. Biomarkers were sampled at inclusion and considered as categorical and continuous variables in Cox proportional hazard models. Results. Mean follow-up ± SD was 926 ± 385 days, during which 52 patients (48%) died. All three markers...

  18. Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Changlin Zhang

    Full Text Available Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE cardiovascular magnetic resonance (CMR, in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP and cardiac troponin I (cTnI to identify LGE-CMR in patients with HOCM.Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females. Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis.LGE was detected in 120 of 163 patients (73.6%. Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6-2340.8] vs. 866.6 [707.2-1875.2] pmol/L, P = 0.003; 0.024 [0.010-0.049] vs. 0.010 [0.005-0.021] ng/ml, P <0.001, respectively. The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001 and log NT-proBNP (r = 0.211, P = 0.007. On multivariable analysis, both log cTnI and maximum wall thickness (MWT were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively, whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025 ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%.Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM.

  19. N-terminal Pro-B type natriuretic peptide as long-term predictor of death after an acute pulmonary embolism.

    Science.gov (United States)

    Alonso-Martínez, José Luis; Annicchérico-Sánchez, Francisco Javier; Urbieta-Echezarreta, Miren Aránzazu; Pérez-Ricarte, Sara

    2015-03-15

    After an acute pulmonary embolism few long-term prognostic factors have shown to be of practical use. We hypothesized that, as in heart failure, natriuretic peptides could serve as biomarkers of a late deleterious prognosis. Consecutive patients admitted to an Internal Medicine ward diagnosed with acute pulmonary embolism were traced through the computerized system of clinical episodes of Navarra Health System and by telephone calls. On hospitalization, standard evaluation was made, previous history of cancer and cardiac disease was recorded, and N-terminal ProB-type natriuretic peptide (NT-ProBNP), D-dimer and Troponin I were measured. In the analysis all-causes death was considered. Two hundred and thirty-four patients were traced, median age 75 [interquartile range (IQR) 16] years old, women 51%. At a median time of 9.5 (IQR 29) months 52 (22%) patients had died, 38 (73%) dead patients had NT-ProBNP higher than 850 ng/L. NT-ProBNP in dead patients was 2.741 (IQR 7.420)ng/L and 662 (IQR 2.517)ng/L in survivors (p<0.001). Age (OR 4.37 CI 95% 1.04-1.16) and NT-ProBNP (OR 1.49 CI 95% 1-1.002) showed to be independent factors of mortality. Between the 3rd and 20th month after the diagnosis, a level of NT-ProBNP higher than 850 ng/L (sensitivity 0.86, specificity 0.45 and negative predictive value 0.92) was associated with a lower survival (p=0.019), hazard ratio 1.89, OR 7.67 (CI 95% 1.52-39.44) for this period. Besides the unchangeable age, plasma level of NT-ProBNP measured on acute pulmonary embolism could predict longer-term all-cause death. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  20. N-terminal pro-brain natriuretic peptide and exercise capacity in chronic heart failure: data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study.

    Science.gov (United States)

    Felker, G Michael; Whellan, David; Kraus, William E; Clare, Robert; Zannad, Faiez; Donahue, Mark; Adams, Kirkwood; McKelvie, Robert; Piña, Ileana L; O'Connor, Christopher M

    2009-10-01

    To examine the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and exercise capacity in a large contemporary cohort of patients with chronic heart failure. Natriuretic peptides such as NT-proBNP are important biomarkers in heart failure. The relationship between NT-proBNP and exercise capacity has not been well studied. We analyzed the relationship between baseline NT-proBNP and peak oxygen uptake (peak VO(2)) or distance in the 6-minute walk test in 1383 subjects enrolled in the HF-ACTION study. Linear regression models were used to analyze the relationship between NT-proBNP and peak Vo(2) or distance in the 6-minute walk test in the context of other clinical variables. Receiver operator curve analysis was used to evaluate the ability of NT-proBNP to accurately predict a peak VO(2) <12 mL/kg per minute. NT-proBNP was the most powerful predictor of peak VO(2) (partial R(2) = 0.13, P < .0001) of 35 candidate variables. Although NT-proBNP was also a predictor of distance in the 6-minute walk test, this relationship was weaker than that for peak VO(2) (partial R(2) = 0.02, P < .0001). For both peak VO(2) and distance in the 6-minute walk test, much of the variability in exercise capacity remained unexplained by the variables tested. Receiver operator curve analysis suggested NT-proBNP had moderate ability to identify patients with peak VO(2) <12 mL/kg per minute (c-index, 0.69). In this analysis of baseline data from HF-ACTION, NT-proBNP was the strongest predictor of peak VO(2) and a significant predictor of distance in the 6-minute walk test. Despite these associations, NT-proBNP demonstrated only modest performance in identifying patients with a low peak VO(2) who might be considered for cardiac transplantation. These data suggest that, although hemodynamic factors are important determinants of exercise capacity, much of the variability in exercise performance in heart failure remains unexplained by traditional clinical and demographic

  1. Islet transplantation in diabetic rats normalizes basal and exercise-induced energy metabolism

    NARCIS (Netherlands)

    Houwing, Harmina; Benthem, L.; Suylichem, P.T.R. van; Leest, J. van der; Strubbe, J.H.; Steffens, A.B.

    Transplantation of islets of Langerhans in diabetic rats normalizes resting glucose and insulin levels, but it remains unclear whether islet transplantation restores resting and exercise-induced energy metabolism. Therefore, we compared energy metabolism in islet transplanted rats with energy

  2. BNP and NT-proBNP Test

    Science.gov (United States)

    ... Culture Blood Gases Blood Ketones Blood Smear Blood Typing Blood Urea Nitrogen (BUN) BNP and NT-proBNP ... Luteinizing Hormone (LH) Lyme Disease Tests Magnesium Maternal Serum Screening, Second Trimester Measles and Mumps Tests Mercury ...

  3. EXERCISE-INDUCED ARTERIAL ADAPTATIONS IN ELITE JUDO ATHLETES

    Directory of Open Access Journals (Sweden)

    Panagiotis Karagounis

    2009-09-01

    Full Text Available The purpose of this study was to examine exercise-induced arterial adaptations in elite Judo male and female athletes. 27 male Judo athletes (age 24.06 ± 2 years, 11 female Judoka (age 24.27 ± 1 years, 27 sedentary healthy men (age 24.01 ± 2 years and 11 women (age 24.21 ± 1 years participated in the current study. The examined vessels included brachial, radial, ulnar, popliteal, anterior and posterior tibial arteries. The experimental parameters were recorded with the use of Duplex ultrasound at rest. Diastolic diameter and blood mean flow velocity of the examined arteries in Judo athletes were found to be both significantly increased (p < 0.05 compared to the findings of the control groups. In male Judo athletes the brachial (p < 0.001, radial (p < 0.001, and anterior tibial artery (p < 0.001 presented the highest difference on the diastolic diameter, compared with the control male group. In female Judo athletes, ulnar (p < 0.001, radial (p < 0.001, and brachial (p < 0.001 arteries illustrated the highest diastolic diameter. The highest blood mean flow velocity was recorded in ulnar (p < 0.001 and popliteal arteries (p < 0.001 of the Judo athletes groups. Recording differences between the two genders, male participants presented larger arteries than females. Conclusively, Judo has been found to be a highly demanding physical sport, involving upper and lower limbs leading to significant arterial adaptations. Obtaining vascular parameters provide a useful tool to the medical team, not only in the direction of enhancement of the efficacy of physical training, but in unknown so far parameters that may influence athletic performance of both male and female elite Judokas

  4. Exercise-induced bronchospasm among school children in Gusau, Nigeria.

    Science.gov (United States)

    Onazi, S O; Orogade, A A; Yakubu, A M

    2012-01-01

    Childhood asthma was said to be rare in Northern Nigeria three decades ago. However, since then, there has been rapid industrial development with increase in especially textile and quarry factories. Hyperresponsiveness of the bronchi of asthmatic children to various challenge tests differentiate them from non-asthmatic children. One of these, the Exercise-Induced Bronchospasm (EIB) which is a reduction in post exercise Peak Expiratory Flow Rate (PEFR), is widely used to define childhood asthma in epidemiological studies. To determine the current prevalence of asthma in childhood in a Northwestern Nigerian town, pupils aged 5-14 years were enrolled in the study. A modified ISAAC questionnaire was administered and the subjects trained to use the peak flow meter. Pre exercise PEFR was obtained thereafter they were subjected to a six minute free running exercise challenge test and the best of three post exercise PEFR taken at intervals was obtained. EIB was taken as 15% reduction or more in post-exercise compared to pre-exercise PEFR. The prevalence of EIB was 6.0% (64/1067 subjects) while 12.7% (136/1067) had a history of wheeze. History of wheeze was found to be a sensitive (96.3%) but nonspecific (22.2%) indicator of childhood asthma. The highest prevalence of EIB was among children aged 10-14 years with male: female ratio 1.9:1. The location of the residence of the pupils did not significantly affect the prevalence of EIB. The prevalence of childhood asthma in this region is on the increase compared to earlier studies and there should be a high index of suspicion in children with suggestive symptoms who should then undergo further screening tests.

  5. Exercise-induced arteriovenous intrapulmonary shunting in dogs.

    Science.gov (United States)

    Stickland, Michael K; Lovering, Andrew T; Eldridge, Marlowe W

    2007-08-01

    We have previously shown, using contrast echocardiography, that intrapulmonary arteriovenous pathways are inducible in healthy humans during exercise; however, this technique does not allow for determination of arteriovenous vessel size or shunt magnitude. The purpose of this study was to determine whether large-diameter (more than 25 microm) intrapulmonary arteriovenous pathways are present in the dog, and whether exercise recruits these conduits. Through the right forelimb, 10.8 million 25-microm stable isotope-labeled microspheres (BioPAL, Inc., Worcester, MA) were injected either at rest (n = 8) or during high-intensity exercise (6- 8 mph, 10-15% grade, n = 6). Systemic arterial blood was continuously sampled during and for 3 minutes after injection. After euthanasia, tissue samples were obtained from the heart, liver, kidney, and skeletal muscle. In addition, 25- and 50-microm microspheres were infused into four isolated dog lungs that were ventilated and perfused at constant pressures similar to exercise. Blood and tissue samples were commercially analyzed for the presence of microspheres. No microspheres were detected in the arterial blood or tissue samples from resting dogs. In contrast, five of six exercising dogs showed evidence of exercise-induced intrapulmonary arteriovenous shunting, as microspheres were detected in arterial blood and/or tissue. Furthermore, shunt magnitude was calculated to be 1.4 +/- 0.8% of cardiac output (n = 3). Evidence of intrapulmonary arteriovenous anastomoses was also found in three of four isolated lungs. Consistent with previous human findings, these data demonstrate that intrapulmonary arteriovenous pathways are functional in the dog and are recruited with exercise.

  6. Exercise-induced Bronchoconstriction with Firefighting Contained Breathing Apparatus.

    Science.gov (United States)

    Seccombe, Leigh M; Buddle, Lachlan; Brannan, John D; Peters, Matthew J; Farah, Claude S

    2018-02-01

    Protective self-contained breathing apparatus (SCBA) used for firefighting delivers decompressed (cold) dehumidified air that may enhance the severity of exercise-induced bronchoconstriction (EIB) in those susceptible. We investigated the effect of SCBA during exercise on airway caliber in people with asthma and healthy controls. Two exercise challenges (EC) designed to elicit EIB were performed on separate days within 1 wk. The initial challenge was breathing room air (ECRA) with workload titrated to elicit >60% estimated maximum voluntary ventilation. The exercise intensity was repeated for the second challenge using SCBA (ECSCBA). Forced expiratory volume in 1 s (FEV1) was measured before and up to 20 min after exercise. Bronchial hyperresponsivenss (BHR) to the hyperosmolar mannitol test was measured in the subjects with asthma. Twenty subjects with current asthma (mean [SD]: age 27 [6] yr) and 10 healthy controls (31 [5] yr, P = 0.1) were studied. The percent fall in FEV1 after ECSCBA was greater in the mannitol-positive asthma subjects (14.4% [15.1%]) compared with mannitol-negative asthmatic subjects (1.6% [1.7%]; P = 0.02) and controls (2.3% [2.3%]; P = 0.04). The FEV1 response was not different between ECRA and ECSCBA (0.49% [5.57%]; P = 0.6). No BHR to mannitol (n = 7) was highly sensitive for identifying a negative response to ECSCBA (negative predictive value 100%). The SCBA does not increase the propensity or severity for EIB in subjects with BHR. Those subjects with asthma but no BHR to inhaled mannitol did not exhibit EIB. The BHR to a hyperosmolar stimulus maybe considered a useful screening tool for potential recruits with a history of asthma.

  7. Exercise-induced albuminuria is related to metabolic syndrome.

    Science.gov (United States)

    Greenberg, Sharon; Shenhar-Tsarfaty, Shani; Rogowski, Ori; Shapira, Itzhak; Zeltser, David; Weinstein, Talia; Lahav, Dror; Vered, Jaffa; Tovia-Brodie, Oholi; Arbel, Yaron; Berliner, Shlomo; Milwidsky, Assi

    2016-06-01

    Microalbuminuria (MA) is a known marker for endothelial dysfunction and future cardiovascular events. Exercise-induced albuminuria (EiA) may precede the appearance of MA. Associations between EiA and metabolic syndrome (MS) have not been assessed so far. Our aim was to investigate this association in a large sample of apparently healthy individuals with no baseline albuminuria. This was a cross-sectional study of 2,027 adults with no overt cardiovascular diseases who took part in a health survey program and had no baseline MA. Diagnosis of MS was based on harmonized criteria. All patients underwent an exercise test (Bruce protocol), and urinary albumin was measured before and after the examination. Urinary albumin-to-creatinine ratio (ACR) values before and after exercise were 0.40 (0.21-0.89) and 1.06 (0.43-2.69) mg/g for median (interquartile range) respectively. A total of 394 (20%) subjects had EiA; ACR rose from normal rest values (0.79 mg/g) to 52.28 mg/g after exercise (P metabolic equivalents (P < 0.001), higher baseline blood pressure (P < 0.001), and higher levels of fasting plasma glucose, triglycerides, and body mass index (P < 0.001). Multivariate binary logistic regression model showed that subjects with MS were 98% more likely to have EiA (95% confidence interval: 1.13-3.46, P = 0.016). In conclusion, EiA in the absence of baseline MA is independently related to MS. Copyright © 2016 the American Physiological Society.

  8. Exercise-induced bronchospasm, asthma control, and obesity.

    Science.gov (United States)

    Ostrom, Nancy K; Parsons, Jonathan P; Eid, Nemr S; Craig, Timothy J; Stoloff, Stuart; Hayden, Mary Lou; Colice, Gene L

    2013-01-01

    Exercise-induced bronchospasm (EIB) commonly affects patients with asthma. However, the relationship between EIB and asthma control remains unclear. Exercise limitation due to asthma might lead to reduced physical activity, but little information is available regarding obesity and EIB in asthma. A recent survey evaluated the frequency of EIB and exercise-related respiratory symptoms in a large number of patients with asthma. The survey results were reanalyzed to address any relationship between EIB and asthma control and obesity. A nationwide random sample of children aged 4-12 years (n = 250), adolescents aged 13-17 years (n = 266), and adults aged ≥18 years (n = 1001) with asthma were interviewed by telephone. Questions in the survey addressed asthma symptoms in general, medication use, and height and weight. Asthma control was categorized using established methods in the Expert Panel Report 3. Body mass index (BMI) was calculated using standard nomograms and obesity was defined as a BMI ≥ 30 kg/m(2). Most children (77.6%), adolescents (71.1%), and adults (83.1%) had either "not well" or "very poorly" controlled asthma. Children with "not well" controlled asthma reported a history of EIB significantly more often than those with "well" controlled" asthma. Asthma patients of all ages who had "not well" and "very poorly" controlled asthma described multiple (four or more) exercise-related respiratory symptoms significantly more often than those with "well-controlled" asthma. Obesity was significantly more common in adolescents with "not well" and "very poorly" controlled asthma and adults with "very poorly" controlled asthma. Children, adolescents, and adults with asthma infrequently have well-controlled disease. A history of EIB and exercise-related respiratory symptoms occur more commonly in patients with not well and very poorly controlled asthma. Obesity was found more often in adolescents and adults, but not children, with asthma, which was not well and

  9. Exercise-induced bronchoconstriction in rhinitis children without asthma.

    Science.gov (United States)

    Rakkhong, Kasalong; Kamchaisatian, Wasu; Vilaiyuk, Soamarat; Sasisakulporn, Cherapat; Teawsomboonkit, Wanlapa; Pornsuriyasak, Prapaporn; Benjaponpitak, Suwat

    2011-09-01

    Exercise-induced bronchoconstriction (EIB) is a condition that leads to limited participation in sports. Prevalence of EIB ranges from 5-20% in general population to 40 - 90% in asthmatic patients. But the prevalence among rhinitis children with EIB remains debatable. We aimed to determine the prevalence of EIB in nonasthmatic children with rhinitis. A cross-sectional study was performed on 53 rhinitis patients without known asthma who attended the Pediatric Allergy Clinic between March 2009 and February 2010. They all underwent physical examination, skin prick test, pulmonary function tests and an exercise challenge test (ECT) on a treadmill. A positive ECT was defined as a decrease in FEV1 > 10% after exercise. The patients' mean age was 12.3 +/- 2.6 years. Most of them (60.4%) had moderate to severe persistent rhinitis. Eleven out of 53 patients (20.7%) had EIB. The peak time for occurrence of EIB was 10 minutes after exercise. Most of the EIB episodes observed were of mild degree. Patients who had persistent symptoms and a short duration of rhinitis treatment prior to the ECT day had more positive ECT results (72.7% vs. 28.6%, p 0.013, 0.2 years vs.1.9 years, p 0.012, respectively). The history (Hx) was not a reliable means of identifying children who had EIB (ECT+/Hx+ 54.6%, ECT-/Hx+ 54.8%). There was no significant relationship between baseline pulmonary function and the decline in FEV1 after exercise. The prevalence of EIB in rhinitis children without asthma is 20.7%. History, physical examination and pulmonary function are insufficient to diagnose EIB.

  10. Mechanisms and management of exercise-induced asthma in elite athletes

    DEFF Research Database (Denmark)

    Ali, Zarqa; Norsk, Peter; Ulrik, Charlotte Suppli

    2012-01-01

    Asthma is often reported by elite athletes, especially endurance athletes. The aim of this article is to review current knowledge of mechanisms and management of exercise-induced asthma (EIA) in adult elite athletes.......Asthma is often reported by elite athletes, especially endurance athletes. The aim of this article is to review current knowledge of mechanisms and management of exercise-induced asthma (EIA) in adult elite athletes....

  11. N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Mylin, Anne K; Goetze, Jens P; Heickendorff, Lene

    2015-01-01

    AIM: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. MATERIALS & METHODS: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were...... evaluated at specific time-points. RESULTS: N-terminal proCNP concentrations increased with age. High N-terminal proCNP concentrations were associated with high-risk disease and renal impairment. Renal function explained 22% of the variation. N-terminal proCNP concentrations correlated with serum bone ALP...... and serum PINP, but lacked association with bone resorption markers, radiographic bone disease and skeletal-related events. CONCLUSION: Serum N-terminal proCNP are associated with bone formation activity in patients with multiple myeloma, but should be interpreted with caution in patients with renal...

  12. Long-term clinical variation of NT-proBNP in stable chronic heart failure patients

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Kjaer, Andreas

    2007-01-01

    AIMS: Here, the aim is to assess long-term clinical variation (CV) of N-terminal pro-brain natriuretic peptide (NT-proBNP) in stable chronic heart failure (CHF) patients. The proposed use of NT-proBNP for monitoring of CHF patients will require accurate information about long-term CV of the peptide....... METHODS AND RESULTS: Medication, biochemical variables, and NYHA class were recorded at 1-year and 2-year follow-up in patients treated in our heart failure clinic. Only patients without changes in medication and the NYHA class who were not hospitalized or died in the period from first follow-up to 12...... months after the second follow-up were included. A total of 78 patients fulfilled the criteria, and year-to-year CV was calculated to 30% (median) (range: 0-111%) (% changes range: -87 to 397%). Log transformation of NT-proBNP (skewed to the right) reduced the year-to-year CV to 4.7% (range: 0...

  13. Beneficial effects of neuropeptide galanin on reinstatement of exercise-induced somatic and psychological trauma.

    Science.gov (United States)

    He, Biao; Fang, Penghua; Guo, Lili; Shi, Mingyi; Zhu, Yan; Xu, Bo; Bo, Ping; Zhang, Zhenwen

    2017-04-01

    Galanin is a versatile neuropeptide that is distinctly upregulated by exercise in exercise-related tissues. Although benefits from exercise-induced upregulation of this peptide have been identified, many issues require additional exploration. This Review summarizes the information currently available on the relationship between galanin and exercise-induced physical and psychological damage. On the one hand, body movement, exercise damage, and exercise-induced stress and pain significantly increase local and circulatory galanin levels. On the other hand, galanin plays an exercise-protective role to inhibit the flexor reflex and prevent excessive movement of skeletal muscles through enhancing response threshold and reducing acetylcholine release. Additionally, elevated galanin levels can boost repair of the exercise-induced damage in exercise-related tissues, including peripheral nerve, skeletal muscle, blood vessel, skin, bone, articulation, and ligament. Moreover, elevated galanin levels may serve as effective signals to buffer sport-induced stress and pain via inhibiting nociceptive signal transmission and enhancing pain threshold. This Review deepens our understanding of the profitable roles of galanin in exercise protection, exercise injury repair, and exercise-induced stress and pain. Galanin and its agonists may be used to develop a novel preventive and therapeutic strategy to prevent and treat exercise-induced somatic and psychological trauma. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Obesity and Natriuretic Peptides, BNP and NT-proBNP: Mechanisms and Diagnostic Implications for Heart Failure

    OpenAIRE

    Madamanchi, Chaitanya; Alhosaini, Hassan; Sumida, Arihiro; Runge, Marschall S.

    2014-01-01

    Many advances have been made in the diagnosis and management of heart failure (HF) in recent years. Cardiac biomarkers are an essential tool for clinicians: point of care B-Type Natriuretic Peptide (BNP) and its N-terminal counterpart (NT-proBNP) levels help distinguish cardiac from non-cardiac causes of dyspnea and are also useful in the prognosis and monitoring of the efficacy of therapy. One of the major limitations of HF biomarkers is in obese patients where the relationshi...

  15. Expanded Polyglutamine-containing N-terminal Huntingtin Fragments Are Entirely Degraded by Mammalian Proteasomes

    NARCIS (Netherlands)

    Juenemann, Katrin; Schipper-Krom, Sabine; Wiemhoefer, Anne; Kloss, Alexander; Sanz Sanz, Alicia; Reits, Eric A. J.

    2013-01-01

    Huntington disease is a neurodegenerative disorder caused by an expanded polyglutamine (polyQ) repeat within the protein huntingtin (Htt). N-terminal fragments of the mutant Htt (mHtt) proteins containing the polyQ repeat are aggregation-prone and form intracellular inclusion bodies. Improving the

  16. Modulation of mutant huntingtin N-terminal cleavage and its effect on aggregation and cell death

    NARCIS (Netherlands)

    Juenemann, Katrin; Weisse, Christina; Reichmann, Denise; Kaether, Christoph; Calkhoven, Cornelis F.; Schilling, Gabriele

    2011-01-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion near the N-terminus of huntingtin. A neuropathological hallmark of Huntington's disease is the presence of intracellular aggregates composed of mutant huntingtin N-terminal fragments in human postmortem

  17. The membranotropic activity of N-terminal peptides from the pore ...

    Indian Academy of Sciences (India)

    The membranotropic activity of N-terminal peptides from the pore-forming proteins sticholysin I and II is modulated by hydrophobic and electrostatic interactions ... Center for Protein Studies, Biology Faculty, University of Havana, Havana, Cuba; Department of Applied Physics, Institute of Physics, University of São Paulo, São ...

  18. BNP and N-terminal proBNP are both extracted in the normal kidney

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Jensen, Gorm Boje; Møller, Søren

    2006-01-01

    therefore examined the renal and peripheral extraction of N-terminal proBNP and BNP. Materials and methods The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation...

  19. The influence of the N-terminal region of antimicrobial peptide pleurocidin on fungal apoptosis.

    Science.gov (United States)

    Choi, Hyemin; Lee, Dong Gun

    2013-10-28

    In our previous study, the 25-mer antimicrobial peptide pleurocidin (Ple) had been thought to induce apoptosis in Candida albicans. This study demonstrated that reactive oxygen species (ROS) production was a major cause of Ple-induced apoptosis. Four truncated analogs were synthesized to understand the functional roles in the N- and C-terminal regions of Ple on the apoptosis. Ple, Ple (4-25), Ple (1-22), and Ple (1-19) produced ROS, including hydroxyl radicals, on the order of [Ple > Ple (1-22) > Ple (4-25) > Ple (1-19)], whereas Ple (7-25) did not induce any ROS production. The results suggested that the N-terminal deletion affected the ROS-inducing activities much more than that of the C-terminal deletion, and net hydrophobicity [Ple > Ple (1-22) > Ple (4-25) > Ple (1-19) > Ple (7-25)] was related to ROS generation rather than other primary factors like net charge. Hence, we focused on the N-terminal-truncated peptides, Ple (4-25) and Ple (7-25), and examined other apoptotic features, including mitochondrial membrane depolarization, caspase activation, phosphatidylserine externalization, and DNA and nuclear fragmentation. The results also confirmed the disappearance of apoptotic activity of Ple (7-25) by the truncation of the N-terminal region (1-6) and the specific activity patterns between Ple and analogs. In conclusion, the N-terminal region of Ple played an important role in apoptosis.

  20. The membranotropic activity of N-terminal peptides from the pore ...

    Indian Academy of Sciences (India)

    ... activity of N-terminal peptides from the pore-forming proteins sticholysin I and II is modulated by hydrophobic and electrostatic interactions as well as lipid composition. Uris Ros Lohans Pedrera Daylín Díaz Juan C De Karam Tatiane P Sudbrack Pedro A Valiente Diana Martínez Eduardo M Cilli Fabiola Pazos Rosangela ...

  1. Molecular dynamics simulations of N-terminal peptides from a nucleotide binding protein

    NARCIS (Netherlands)

    van der Spoel, D.; Vogel, H.J.; Berendsen, H.J.C.

    Molecular dynamics (MD) simulations of N-terminal peptides from lactate dehydrogenase (LDH) with increasing length and individual secondary structure elements were used to study their stability in relation to folding, Ten simulations of 1-2 ns of different peptides in water starting from the

  2. Evaluation of NT-proBNP concentrations during exercise in asymptomatic patients with severe high-gradient aortic stenosis.

    Science.gov (United States)

    Dobrowolski, Piotr; Lech, Agnieszka; Klisiewicz, Anna; Hoffman, Piotr

    2016-08-11

    INTRODUCTION The effect of asymptomatic severe aortic stenosis (ASAS) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels ar rest and during exercise, as well as their relevance for clinical practice remain controversial.  OBJECTIVES The aim of this study was to test the hypothesis of whether the evaluation of NT-proBNP concentrations during exercise provides additional information about the severity of aortic stenosis and left ventricular remodeling in patients with ASAS. PATIENTS AND METHODS A total of 50 patients with ASAS (mean age, 38.4 ±18.1 years) and 21 healthy subjects (mean age, 43.4 ±10.6 years) were enrolled. Rest and exercise echocardiography was performed to evaluate maximum velocity (Vmax), mean aortic gradient (AG), and aortic valve area (AVA). The left ventricular mass index (LVMI) was calculated. NT-proBNP concentrations at rest and during exercise were assessed, and the difference between the 2 values was calculated (ΔNT-proBNP). RESULTS NT-proBNP and ΔNT-proBNP levels at rest and during exercise were significantly higher in the ASAS group compared with the control group. In the ASAS group, NT-proBNP levels at rest significantly correlated with LVMI (r = 0.432; P <0.0001), AVA (r = -0.408; P <0.0001), Vmax (r = 0.375; P = 0.002), and mean AG (r = 0.257; P = 0.03). NT-proBNP levels during exercise significantly correlated with LVMI (r = 0.432; P <0.0001), mean AG (r = 0.401; P = 0.001), and AVA (r = -0.375; P = 0.001). In the multivariate logistic regression model, the factors independently associated with NT-proBNP both at rest and during exercise were age, AVA, and LVMI. CONCLUSIONS NT-proBNP levels at rest provide valuable information for identifying patients with more advanced left ventricular hypertrophy secondary to severe aortic stenosis. NT-proBNP levels during exercise do not provide new information on the severity of AS.

  3. Range and distribution of NT-proBNP values in stable corrected congenital heart disease of various types.

    Science.gov (United States)

    Popelová, Jana; Kotaška, Karel; Černý, Stěpán; Prokopová, Milena; Rubáček, Miroslav

    2012-01-01

    Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are an expected finding in many adults with congenital heart disease (ACHD) but no reports have described the range of values within different diagnostic groups. Between the years 2003 and 2011 we measured NT-proBNP in consecutive ACHD patients attending the outpatient department. Further NT-proBNP analysis was performed on 705 blood samples from 394 stable patients with the defect corrected. The results were compared among different diagnostic groups and with a control group of healthy volunteers. The median value of NT-proBNP in the whole cohort was signifinatly higher than in the control group (211 vs 42 pg/mL; P value of NT-proBNP in pg/mL and the percentage of normal NT-proBNP values in the listed diagnostic groups were as follows: coarctation of the aorta (COA), 97 (64%); pulmonary stenosis (PS),160 (48%); secundum atrial septal defect (ASD), 254 (44%); incomplete atrioventricular septal defect (AVSD), 211 (32%); ventricular septal defect (VSD), 154 (58%); tetralogy of Fallot (TOF), 177 (38%); transposition of the great arteries (TGA) after Mustard, 237 (20%) or Senning correction, 143 (39%); Ebstein anomaly 287, (26%); pulmonary atresia (PA), 327 (18%); and complex defects after Fontan procedure, 184 (31%). Normal levels of NT-proBNP were found most often in patients after the correction of coarctation of the aorta and ventricular septal defect with the highest levels found in pulmonary atresia and Ebstein anomaly. Our results may serve as reference values for different ACHD groups. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Differential diagnostic value and prognosis estimation of serum NT-proBNP level in the elderly patients with acute dyspnea

    International Nuclear Information System (INIS)

    Shi Yizhen; Wu Weiyi; Shen Yongmei; Huang Hong; Wang Wei; Rong Guang; Gao Lan

    2009-01-01

    Objective: To study the differential diagnostic value and prognosis estimation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in the elderly patients with acute dyspnea. Methods: Serum level of NT-proBNP were measured with automated electrochemiluminescence immunoassay in 72 dyspneic patients with heart failure (HF) and 54 without HF who were elder than 65 years. It was measured again in 25 patients after therapy. Left ventricular ejection fraction(LVEF) was measured with heart ultrasonic in the same time. Twenty healthy cases were selected as the control group. Results: LVEF of the group with HF was lower than those in the control group (P<0.01), while both median NT-proBNP in the two groups were considerably higher than those in the control group (P<0.01), and levels of NT-proBNP were negatively correlated with LVEF (r = - 0.548, P<0.05). An optimal strategy to identify dyspneic patients with HF was used for ROC curve analysis (area =0.932), which yielded 84% positive predictive value, 91.1%negative predictive value and 86.5% accuracy for dyspneic patients with HF at 1 500 pg/ml cut-off. NT-proBNP levels in 21 patients who had good prognosis decreased significantly. Conclusion: NT-proBNP level is valuable for diagnostic evaluation and short-term prognosis estimation in dyspnoeic patients with suspected or confirmed HF. It is important to establish broader standards of the NT-proBNP in elderly dyspnoeic patients. (authors)

  5. Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide, Troponin-T, and Growth-Differentiation Factor 15 in Adult Congenital Heart Disease.

    Science.gov (United States)

    Baggen, Vivan J M; van den Bosch, Annemien E; Eindhoven, Jannet A; Schut, Anne-Rose W; Cuypers, Judith A A E; Witsenburg, Maarten; de Waart, Monique; van Schaik, Ron H N; Zijlstra, Felix; Boersma, Eric; Roos-Hesselink, Jolien W

    2017-01-17

    The number of patients with adult congenital heart disease (ACHD) is rapidly increasing. To optimize patient management, there is a great need to accurately identify high-risk patients. Still, no biomarker has been firmly established as a clinically useful prognostic tool in this group. We studied the association of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitive troponin-T, and growth-differentiation factor 15 with cardiovascular events in ACHD. Clinically stable patients with ACHD who routinely visited the outpatient clinic between April 2011 and April 2013 underwent clinical assessment, electrocardiography, echocardiography, and biomarker measurement (NT-proBNP, high-sensitive troponin-T, and growth-differentiation factor 15) at the time of study inclusion. Patients were prospectively followed for the occurrence of cardiovascular events (death, heart failure, hospitalization, arrhythmia, thromboembolic events, and reintervention). Survival curves were derived by the Kaplan-Meier method, and Cox regression was performed to investigate the relation between biomarkers and events with adjustment for multiple clinical and echocardiographic variables. In total, 595 patients were included (median age, 33 years; interquartile range, 25-41 years; 58% male; 90% New York Heart Association class I). Patients were followed during a median of 42 (interquartile range, 37-46) months. Of the 3 evaluated biomarkers, NT-proBNP in the upper quartile (>33.3 pmol/L) was most strongly associated with cardiovascular events (n=165, adjusted hazard ratio, 9.05 [3.24-25.3], P14 pmol/L), elevated high-sensitive troponin-T (>14 ng/L), and elevated growth-differentiation factor 15 (>1109 ng/L) identified those patients at highest risk of cardiovascular events (log-rank PT, and growth-differentiation factor 15 identify patients at highest risk of cardiovascular events. These biomarkers therefore may play an important role in the monitoring and management of patients with

  6. Clinical correlation between N-terminal pro-b-type natriuretic peptide and angiographic coronary atherosclerosis

    Directory of Open Access Journals (Sweden)

    Demóstenes G.L. Ribeiro

    2014-06-01

    Full Text Available OBJECTIVES:This study aimed to investigate the clinical correlation between angiographic coronary atherosclerosis and N-terminal pro-B-type natriuretic peptide along with other known correlated factors.METHODS:In total, 153 patients with a diagnostic hypothesis of stable angina, unstable angina or acute myocardial infarction were classified as group A (patients with angiographically normal coronary arteries or group B (patients with angiographic coronary atherosclerosis. The two groups were analyzed with respect to the following factors: gender, age, body mass index, abdominal circumference, smoking, diabetes mellitus, arterial hypertension, early family history of atherosclerosis, statin use, the presence of metabolic syndrome, clinical presentation and biochemical factors, including cholesterol, creatinine and fibrinogen plasma concentrations, monocyte counts and N-terminal pro-B-type natriuretic peptide.RESULTS:Univariate analyses comparing the two groups revealed that group B patients more frequently had diabetes, used statins and had systolic dysfunction, N-terminal pro-B-type natriuretic peptide levels ≥250 pg/mL, fibrinogen levels >500 mg/dL and ≥501 monocytes/mm3 compared with group A patients (p<0.05. Nevertheless, multivariate logistic regression analysis demonstrated that the independent predictors of angiographic coronary atherosclerosis were an N-terminal pro-B-type natriuretic peptide level ≥250 pg/mL, diabetes mellitus and increased monocyte numbers and fibrinogen plasma concentration, regardless of the creatinine level or the presence of systolic dysfunction.CONCLUSIONS:An N-terminal pro-B-type natriuretic peptide plasma concentration of ≥250 pg/mL is an independent predictor of angiographic coronary atherosclerosis.

  7. Site directed spin labeling studies of Escherichia coli dihydroorotate dehydrogenase N-terminal extension

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Sheila G. [Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao-carlense 400, C.P. 369, 13560-970, Sao Carlos, SP (Brazil); Grupo de Biofisica e Fisica Aplicada a Medicina, Instituto de Fisica, Universidade Federal de Goias, Campus Samambaia, C.P. 131, 74001-970, Goiania, GO (Brazil); Cristina Nonato, M. [Laboratorio de Cristalografia de Proteinas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. do Cafe S/N, 14040-903, Ribeirao Preto, SP (Brazil); Costa-Filho, Antonio J., E-mail: ajcosta@ffclrp.usp.br [Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao-carlense 400, C.P. 369, 13560-970, Sao Carlos, SP (Brazil); Departamento de Fisica, Faculdade de Filosofia, Ciencias e Letras de Ribeirao Preto, Av. Bandeirantes 3900, 14040-901, Ribeirao Preto, SP (Brazil)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer EcDHODH is a membrane-associated enzyme and a promising target for drug design. Black-Right-Pointing-Pointer Enzyme's N-terminal extension is responsible for membrane association. Black-Right-Pointing-Pointer N-terminal works as a molecular lid regulating access to the protein interior. -- Abstract: Dihydroorotate dehydrogenases (DHODHs) are enzymes that catalyze the fourth step of the de novo synthesis of pyrimidine nucleotides. In this reaction, DHODH converts dihydroorotate to orotate, using a flavine mononucleotide as a cofactor. Since the synthesis of nucleotides has different pathways in mammals as compared to parasites, DHODH has gained much attention as a promising target for drug design. Escherichia coli DHODH (EcDHODH) is a family 2 DHODH that interacts with cell membranes in order to promote catalysis. The membrane association is supposedly made via an extension found in the enzyme's N-terminal. In the present work, we used site directed spin labeling (SDSL) to specifically place a magnetic probe at positions 2, 5, 19, and 21 within the N-terminal and thus monitor, by using Electron Spin Resonance (ESR), dynamics and structural changes in this region in the presence of a membrane model system. Overall, our ESR spectra show that the N-terminal indeed binds to membranes and that it experiences a somewhat high flexibility that could be related to the role of this region as a molecular lid controlling the entrance of the enzyme's active site and thus allowing the enzyme to give access to quinones that are dispersed in the membrane and that are necessary for the catalysis.

  8. Exercise-induced pulmonary hemorrhage: where are we now?

    Directory of Open Access Journals (Sweden)

    Poole DC

    2016-11-01

    Full Text Available David C Poole,1,2 Howard H Erickson1 1Department of Anatomy and Physiology, 2Department of Kinesiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA Abstract: As the Thoroughbreds race for the final stretch, 44 hooves flash and thunder creating a cacophony of tortured air and turf. Orchestrated by selective breeding for physiology and biomechanics, expressed as speed, the millennia-old symphony of man and beast reaches its climax. At nearly 73 kilometers per hour (45 mph over half a ton of flesh and bone dwarfs its limpet-like jockey as, eyes wild and nostrils flaring, their necks stretch for glory. Beneath each resplendent livery-adorned, latherin-splattered coat hides a monstrous heart trilling at 4 beats per second, and each minute, driving over 400 L (105 gallons of oxygen-rich blood from lungs to muscles. Matching breath to stride frequency, those lungs will inhale 16 L (4 gallons of air each stride moving >1,000 L/min in and out of each nostril – and yet failing. Engorged with blood and stretched to breaking point, those lungs can no longer redden the arterial blood but leave it dusky and cyanotic. Their exquisitely thin blood–gas barrier, a mere 10.5 μm thick (1/50,000 of an inch, ruptures, and red cells invade the lungs. After the race is won and lost, long after the frenetic crowd has quieted and gone, that blood will clog and inflame the airways. For a few horses, those who bleed extensively, it will overflow their lungs and spray from their nostrils incarnadining the walls of their stall: a horrifically poignant canvas that strikes at horse racing’s very core. That exercise-induced pulmonary hemorrhage (EIPH occurs is a medical and physiological reality. That every reasonable exigency is not taken to reduce/prevent it would be a travesty. This review is not intended to provide an exhaustive coverage of EIPH for which the reader is referred to recent reviews, rather, after a brief reminder of its

  9. The NT digital micro tape recorder

    Science.gov (United States)

    Sasaki, Toshikazu; Alstad, John; Younker, Mike

    1993-01-01

    The description of an audio recorder may at first glance seem out of place in a conference which has been dedicated to the discussion of the technology and requirements of mass data storage. However, there are several advanced features of the NT system which will be of interest to the mass storage technologist. Moreover, there are a sufficient number of data storage formats in current use which have evolved from their audio counterparts to recommend a close attention to major innovative introductions of audio storage formats. While the existing analog micro-cassette recorder has been (and will continue to be) adequate for various uses, there are significant benefits to be gained through the application of digital technology. The elimination of background tape hiss and the availability of two relatively wide band channels (for stereo recording), for example, would greatly enhance listenability and speech intelligibility. And with the use of advanced high-density recording and LSI circuit technologies, a digital micro recorder can realize unprecedented compactness with excellent energy efficiency. This is what was accomplished with the NT-1 Digital Micro Recorder. Its remarkably compact size contributes to its portability. The high-density NT format enables up to two hours of low-noise digital stereo recording on a cassette the size of a postage stamp. Its highly energy-efficient mechanical and electrical design results in low power consumption; the unit can be operated up to 7 hours (for continuous recording) on a single AA alkaline battery. Advanced user conveniences include a multifunction LCD readout. The unit's compactness and energy-efficiency, in particular, are attributes that cannot be matched by existing analog and digital audio formats. The size, performance, and features of the NT format are of benefit primarily to those who desire improved portability and audio quality in a personal memo product. The NT Recorder is the result of over ten years of

  10. Risk stratification with the use of serial N-terminal pro-B-type natriuretic peptide measurements during admission and early after discharge in heart failure patients: post hoc analysis of the PRIMA study.

    Science.gov (United States)

    Eurlings, Luc W; Sanders-van Wijk, Sandra; van Kraaij, Dave J W; van Kimmenade, Roland; Meeder, Joan G; Kamp, Otto; van Dieijen-Visser, Marja P; Tijssen, Jan G P; Brunner-La Rocca, Hans-Peter; Pinto, Yigal M

    2014-12-01

    The aim of this work was to assess the prognostic value of absolute N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration in combination with changes during admission because of acute heart failure (AHF) and early after hospital discharge. In AHF, readmission and mortality rates are high. Identifying those at highest risk for events early after hospital discharge might help to select patients in need of intensive outpatient monitoring. We evaluated the prognostic value of NT-proBNP concentration on admission, at discharge, 1 month after hospital discharge and change over time in 309 patients included in the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. Primary outcome measures were mortality and the combined end point of heart failure (HF) readmission or mortality. In a multivariate Cox regression analysis, change in NT-proBNP concentration during admission, change from discharge to 1 month after discharge, and the absolute NT-proBNP concentration at 1 month after discharge were of independent prognostic value for both end points (hazard ratios for HF readmission or mortality: 1.71, 95% confidence interval [CI] 1.13-2.60, Wald 6.4 [P = .011] versus 2.71, 95% CI 1.76-4.17, Wald 20.5 [P < .001] versus 1.81, 95% CI 1.13-2.89, Wald 6.1 [P = .014], respectively. Knowledge of change in NT-proBNP concentration during admission because of AHF in combination with change early after discharge and the absolute NT-proBNP concentration at 1 month after discharge allows accurate risk stratification. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. De Nederlandse Empathie Quotiënt (EQ) en Systematiseren Quotiënt (SQ)

    NARCIS (Netherlands)

    Groen, Yvonne; Fuermaier, Anselm B.M.; den Heijer, Anne E.; Tucha, Oliver; Althaus, Monika

    2016-01-01

    De Empathie Quotiënt (EQ) en de Systematiseren Quotiënt (SQ) zijn wereldwijd gebruikte vragenlijsten om de cognitieve stijl van personen te meten. In een recent gepubliceerde studie [Groen, Y., Fuermaier, A.B.M.,Den Heijer, A.E., Tucha, O., & Althaus, M. (2015). Journal of Autism and Developmental

  12. Cyclization of the N-Terminal X-Asn-Gly Motif during Sample Preparation for Bottom-Up Proteomics

    DEFF Research Database (Denmark)

    Zhang, Xumin; Højrup, Peter

    2010-01-01

    We, herein, report a novel -17 Da peptide modification corresponding to an N-terminal cyclization of peptides possessing the N-terminal motif of X-Asn-Gly. The cyclization occurs spontaneously during sample preparation for bottom-up proteomics studies. Distinct from the two well-known N...

  13. HMC-1 human mast cells synthesize neurotensin (NT) precursor, secrete bioactive NT-like peptide(s) and express NT receptor NTS1.

    Science.gov (United States)

    Cochrane, David E; Carraway, Robert E; Harrington, Kimberly; Laudano, Melissa; Rawlings, Stephen; Feldberg, Ross S

    2011-12-01

    To determine if mast cells synthesize the inflammatory peptide, neurotensin (NT), secrete immunoreactive and bioactive NT, and express the NT receptor NTS1. HMC-1 cells, pleural mast cells from Sprague-Dawley rats, LAD2 mast cells, and human cord blood mast cells were used. HMC-1 cells were stimulated with NT, C48/80, mastoparan, or PGE(2). For changes in cutaneous vascular permeability, anesthetized rats were injected intravenously with Evans Blue dye and intradermally with saline, NT, histamine, diphenhydramine, and C48/80. RT-PCR was used to identify RNA transcripts. Histamine was measured by fluorometric assay. In vivo cutaneous vascular permeability assays, radio-immunoassays for NT, Western blotting for the NT precursor protein and NTS1 protein from HMC-1 cells and tissues from rats were used. Immunohistochemistry was used to identify NT precursor-like proteins in HMC-1 mast cells. HMC-1 cells express mRNAs for NT precursor, PC5A processing enzyme and NTS1 receptor. Human cord blood mast cells and LAD2 mast cells express mRNA transcripts for NT precursor and NTS1. Western blotting showed NT precursor and NTS1 receptor in HMC1. Rat tissues with high numbers of mast cells contained NT precursor proteins. NT-like peptides from HMC-1 displayed NT-like bioactivity. HMC-1 mast cells synthesize and secrete immunoreactive and bioactive NT-like peptide(s) and express the NT receptor, suggesting that NT from mast cells might serve autocrine and paracrine roles.

  14. Regulation of presynaptic Ca2+, synaptic plasticity and contextual fear conditioning by a N-terminal β-amyloid fragment.

    Science.gov (United States)

    Lawrence, James L M; Tong, Mei; Alfulaij, Naghum; Sherrin, Tessi; Contarino, Mark; White, Michael M; Bellinger, Frederick P; Todorovic, Cedomir; Nichols, Robert A

    2014-10-22

    Soluble β-amyloid has been shown to regulate presynaptic Ca(2+) and synaptic plasticity. In particular, picomolar β-amyloid was found to have an agonist-like action on presynaptic nicotinic receptors and to augment long-term potentiation (LTP) in a manner dependent upon nicotinic receptors. Here, we report that a functional N-terminal domain exists within β-amyloid for its agonist-like activity. This sequence corresponds to a N-terminal fragment generated by the combined action of α- and β-secretases, and resident carboxypeptidase. The N-terminal β-amyloid fragment is present in the brains and CSF of healthy adults as well as in Alzheimer's patients. Unlike full-length β-amyloid, the N-terminal β-amyloid fragment is monomeric and nontoxic. In Ca(2+) imaging studies using a model reconstituted rodent neuroblastoma cell line and isolated mouse nerve terminals, the N-terminal β-amyloid fragment proved to be highly potent and more effective than full-length β-amyloid in its agonist-like action on nicotinic receptors. In addition, the N-terminal β-amyloid fragment augmented theta burst-induced post-tetanic potentiation and LTP in mouse hippocampal slices. The N-terminal fragment also rescued LTP inhibited by elevated levels of full-length β-amyloid. Contextual fear conditioning was also strongly augmented following bilateral injection of N-terminal β-amyloid fragment into the dorsal hippocampi of intact mice. The fragment-induced augmentation of fear conditioning was attenuated by coadministration of nicotinic antagonist. The activity of the N-terminal β-amyloid fragment appears to reside largely in a sequence surrounding a putative metal binding site, YEVHHQ. These findings suggest that the N-terminal β-amyloid fragment may serve as a potent and effective endogenous neuromodulator. Copyright © 2014 the authors 0270-6474/14/3414210-09$15.00/0.

  15. Elevated NT-proBNP is associated with unfavorably altered plasma fibrin clot properties in atrial fibrillation.

    Science.gov (United States)

    Matusik, Paweł T; Matusik, Patrycja S; Kornacewicz-Jach, Zdzisława; Małecka, Barbara; Ząbek, Andrzej; Undas, Anetta

    2017-09-15

    Dense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF. We investigated plasma fibrin clot permeability (K s ), clot lysis time (CLT), endogenous thrombin potential (ETP) as well as other coagulation and fibrinolysis parameters along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in 160 AF patients (median age, 70.5years). Previous stroke (n=15; 9.4%) was associated with decreased K s (P=0.04) and longer CLT (P=0.005), together with higher antiplasmin (P=0.03) and lower tissue-type plasminogen activator (P=0.01). Lower K s (P=0.04) and tendency towards longer CLT (P=0.10) were observed in patients with a left atrium diameter>40mm. Patients with a CHA 2 DS 2 -VASc score of 3 or more (82.5%) were characterized by higher thrombin-activatable fibrinolysis inhibitor antigen (P=0.009). K s was inversely correlated with log NT-proBNP (r=-0.34, PCLT was positively correlated with log NT-proBNP (R=0.61, PCLT (the top quartile,≥109min). In AF patients prothrombotic fibrin clot properties assessed ex vivo are determined by PAI-1 and NT-proBNP and this phenotype is associated with prior ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The role of N-terminal phosphorylation on Huntingtin oligomerization, aggregation and toxicity

    OpenAIRE

    Santos, Joana Margarida Marques Branco dos, 1987-

    2012-01-01

    Tese de mestrado, Neurociências, Faculdade de Medicina, Universidade de Lisboa, 2012 Huntington’s disease (HD) is a hereditary disorder caused by a mutation in the exon-1 of the IT-15 gene, which encodes for a protein called huntingtin. The N-terminal region of mutant huntingtin is prone to aggregate and is toxic for specific types of neurons in the striatum and cortex, leading to the involuntary movements and psychiatric disturbances that characterize HD. Growing evidence indicates that t...

  17. N-terminal PDZ-like domain of chromatin organizer SATB1 ...

    Indian Academy of Sciences (India)

    as a global repressor via recruitment of CtBP1:HDAC1-containing co-repressors to its binding targets. The. N-terminal PSD95/Dlg-A/ZO-1 (PDZ)-like domain of SATB1 mediates interactions with several chromatin proteins. In the present study, we set out to address whether the PDZ-domain-mediated interactions of SATB1 ...

  18. Jun N-terminal protein kinase enhance middle ear mucosal proliferation during bacterial otitis media

    OpenAIRE

    Furukawa, Masayuki; Ebmayer, Jörg; Pak , Kwang; Austin, Darrell A.; Melhus , Åsa; Webster, Nicholas J. G.; Ryan, Allen F.

    2007-01-01

    Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but pa...

  19. Receptor binding and adenylate cyclase activities of glucagon analogues modified in the N-terminal region

    International Nuclear Information System (INIS)

    McKee, R.L.; Pelton, J.T.; Trivedi, D.; Johnson, D.G.; Coy, D.H.; Sueiras-Diaz, J.; Hruby, V.J.

    1986-01-01

    In this study, we determined the ability of four N-terminally modified derivatives of glucagon, [3-Me-His1,Arg12]-, [Phe1,Arg12]-, [D-Ala4,Arg12]-, and [D-Phe4]glucagon, to compete with 125I-glucagon for binding sites specific for glucagon in hepatic plasma membranes and to activate the hepatic adenylate cyclase system, the second step involved in producing many of the physiological effects of glucagon. Relative to the native hormone, [3-Me-His1,Arg12]glucagon binds approximately twofold greater to hepatic plasma membranes but is fivefold less potent in the adenylate cyclase assay. [Phe1,Arg12]glucagon binds threefold weaker and is also approximately fivefold less potent in adenylate cyclase activity. In addition, both analogues are partial agonists with respect to adenylate cyclase. These results support the critical role of the N-terminal histidine residue in eliciting maximal transduction of the hormonal message. [D-Ala4,Arg12]glucagon and [D-Phe4]glucagon, analogues designed to examine the possible importance of a beta-bend conformation in the N-terminal region of glucagon for binding and biological activities, have binding potencies relative to glucagon of 31% and 69%, respectively. [D-Ala4,Arg12]glucagon is a partial agonist in the adenylate cyclase assay system having a fourfold reduction in potency, while the [D-Phe4] derivative is a full agonist essentially equipotent with the native hormone. These results do not necessarily support the role of an N-terminal beta-bend in glucagon receptor recognition. With respect to in vivo glycogenolysis activities, all of the analogues have previously been reported to be full agonists

  20. Accessibility of the Shine-Dalgarno sequence dictates N-terminal codon bias in E. coli

    OpenAIRE

    Shakhnovich, Eugene; Zhang, Wenli; Yan, Jin; Adkar, Bharat; Jacobs, William; Bhattacharyya, Sanchari; Adkar, Bharat

    2018-01-01

    Despite considerable efforts, no physical mechanism has been shown to explain N-terminal codon bias in prokaryotic genomes. Using a systematic study of synonymous substitutions in two endogenous E. coli genes, we show that interactions between the coding region and the upstream Shine-Dalgarno (SD) sequence modulate the efficiency of translation initiation, affecting both intracellular mRNA and protein levels due to the inherent coupling of transcription and translation in E. coli. We further ...

  1. Fasting glucose, NT-proBNP, treatment with eptifibatide, and outcomes in non-ST-segment elevation acute coronary syndromes: An analysis from EARLY ACS.

    Science.gov (United States)

    Farhan, Serdar; Clare, Robert M; Jarai, Rudolf; Giugliano, Robert P; Lokhnygina, Yuliya; Harrington, Robert A; Kristin Newby, L; Huber, Kurt

    2017-04-01

    Higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels have been linked to a more favorable glucometabolic profile. Little is known about the interaction of NT-proBNP and fasting glucose in non-ST-segment elevation acute coronary syndrome (NSTE ACS). Fasting glucose and NT-proBNP were measured in 2240 patients enrolled in the EARLY ACS trial. Multivariable Cox models were used to assess associations between fasting glucose and NT-proBNP and a 96-hour composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout; 30-day death or MI; and 1-year mortality. In adjusted Cox models, neither NT-proBNP nor fasting glucose was associated with the 96-hour endpoint (p=0.95 and p=0.87). NT-proBNP was associated with 30-day death or MI (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.02-1.22, p=0.02) and 1-year mortality (HR 1.63, 95% CI 1.42-1.89, pfasting glucose was associated only with 1-year death (HR 1.53, 95% CI 1.08-2.16, p=0.02). NT-proBNP×glucose interaction terms were non-significant in all models. As fasting glucose levels increased, the risk of 96-hour and 30-day endpoints increased among patients who received early eptifibatide but not delayed, provisional use (p int =0.035 and p int =0.029). Higher NT-proBNP levels were associated with greater 30-day death or MI among patients who received early eptifibatide but not delayed, provisional use (p int =0.045). NT-proBNP and fasting glucose concentrations were associated with intermediate-term ischemic outcomes and may identify differential response to treatment with eptifibatide. CLINICALTRIALS. NCT00089895. Copyright © 2017. Published by Elsevier B.V.

  2. NT-proBNP as Early Marker of Subclinical Late Cardiotoxicity after Doxorubicin Therapy and Mediastinal Irradiation in Childhood Cancer Survivors

    Directory of Open Access Journals (Sweden)

    Amal Zidan

    2015-01-01

    Full Text Available Background. Childhood cancer survivors treated with anthracyclines and mediastinal irradiation are at risk for late onset cardiotoxicity. Aims of the Study. To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP and tissue Doppler imaging (TDI as early predictors of late onset cardiotoxicity in asymptomatic survivors of childhood cancer treated with doxorubicin with or without mediastinal irradiation. Methods. A cross-sectional study on 58 asymptomatic survivors of childhood cancer who received doxorubicin in their treatment protocols and 32 asymptomatic Hodgkin’s lymphoma survivors who received anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and conventional echocardiography were determined. Results. Thirty percent of survivors had abnormal NT-proBNP levels. It was significantly related to age at diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI detected myocardial affection in 20% more than conventional echocardiography. Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy. Conclusions. TDI could detect early cardiac dysfunction even in those with normal conventional echocardiography. Measurement of NT-proBNP represents an interesting strategy for detecting subclinical cardiotoxicity. We recommend prospective and multicenter studies to validate the role of NT-proBNP as an early marker for late onset doxorubicin-induced cardiotoxicity.

  3. [Adenovirus-mediated killing of hepatocellular carcinoma HepG2 cells by heterogeneous fusion gene NT4p53(N15)Ant].

    Science.gov (United States)

    Li, Yue-ping; Qiu, Shu-dong; Song, Li-ping; Wang, Quan-ying; Yang, Guang-xiao

    2007-07-01

    OBJECTIVE To construct a recombinant adenovirus Ad.NT4p53(N15)Ant and explore its cytotoxic effect against hepatocellular carcinoma HepG2 cells in vitro. The recombinant adenovirus containing the fusion gene of neurotrophin 4 (NT4)signal peptide, N-terminal residues (12-26) of p53 and 17 amino acid Drosophila homeobox protein Antennapedia (Ant) was constructed by gene cloning protocol. The effect of this fusion gene on HepG2 cells was evaluated by MTT assay, PI staining and flow cytometry. The fusion gene Ad.NT4p53(N15)Ant was successfully constructed, as verified by restriction endonuclease digestion and PCR. Ad.NT4p53(N15)Ant could strongly suppress the growth of HepG2 cells (with a growth inhibition rate of 63.3% 48 h after infection) without affecting NIH-3T3 cells. Flow cytometry showed that Ad.NT4p53(N15)Ant could induce obvious apoptosis of HepG2 cells. The recombinant adenovirus containing NT4p53(N15)Ant fusion gene can inhibit the growth the of HepG2 cells in vitro partially by inducing cell apoptosis.

  4. N-terminally truncated POM121C inhibits HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Hideki Saito

    Full Text Available Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1. These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication.

  5. N-terminally truncated POM121C inhibits HIV-1 replication

    Science.gov (United States)

    Saito, Hideki; Masuda, Takao; Noda, Takeshi; Yamaoka, Shoji

    2017-01-01

    Recent studies have identified host cell factors that regulate early stages of HIV-1 infection including viral cDNA synthesis and orientation of the HIV-1 capsid (CA) core toward the nuclear envelope, but it remains unclear how viral DNA is imported through the nuclear pore and guided to the host chromosomal DNA. Here, we demonstrate that N-terminally truncated POM121C, a component of the nuclear pore complex, blocks HIV-1 infection. This truncated protein is predominantly localized in the cytoplasm, does not bind to CA, does not affect viral cDNA synthesis, reduces the formation of 2-LTR and diminished the amount of integrated proviral DNA. Studies with an HIV-1-murine leukemia virus (MLV) chimeric virus carrying the MLV-derived Gag revealed that Gag is a determinant of this inhibition. Intriguingly, mutational studies have revealed that the blockade by N-terminally-truncated POM121C is closely linked to its binding to importin-β/karyopherin subunit beta 1 (KPNB1). These results indicate that N-terminally-truncated POM121C inhibits HIV-1 infection after completion of reverse transcription and before integration, and suggest an important role for KPNB1 in HIV-1 replication. PMID:28873410

  6. Structure of the human histone chaperone FACT Spt16 N-terminal domain

    International Nuclear Information System (INIS)

    Marcianò, G.; Huang, D. T.

    2016-01-01

    The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding

  7. Structure of the human histone chaperone FACT Spt16 N-terminal domain

    Energy Technology Data Exchange (ETDEWEB)

    Marcianò, G.; Huang, D. T., E-mail: d.huang@beatson.gla.ac.uk [Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland (United Kingdom)

    2016-01-22

    The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.

  8. Copper(II) Binding Sites in N-Terminally Acetylated α-Synuclein: A Theoretical Rationalization.

    Science.gov (United States)

    Ramis, Rafael; Ortega-Castro, Joaquín; Vilanova, Bartolomé; Adrover, Miquel; Frau, Juan

    2017-08-03

    The interactions between N-terminally acetylated α-synuclein and Cu(II) at several binding sites have been studied with DFT calculations, specifically with the M06 hybrid functional and the ωB97X-D DFT-D functional. In previous experimental studies, Cu(II) was shown to bind several α-synuclein residues, including Met1-Asp2 and His50, forming square planar coordination complexes. Also, it was determined that a low-affinity binding site exists in the C-terminal domain, centered on Asp121. However, in the N-terminally acetylated protein, present in vivo, the Met1 site is blocked. In this work, we simplify the representation of the protein by modeling each experimentally found binding site as a complex between an N-terminally acetylated α-synuclein dipeptide (or several independent residues) and a Cu(II) cation, and compare the results with a number of additional, structurally analogous sites not experimentally found. This way of representing the binding sites, although extremely simple, allows us to reproduce experimental results and to provide a theoretical rationale to explain the preference of Cu(II) for certain sites, as well as explicit geometrical structures for the complexes formed. These results are important to understand the interactions between α-synuclein and Cu(II), one of the factors inducing structural changes in the protein and leading to aggregated forms of it which may play a role in neurodegeneration.

  9. AnNPPBPromoter Polymorphism Associated With Elevated N-Terminal pro-B-Type Natriuretic Peptide and Lower Blood Pressure, Hypertension, and Mortality.

    Science.gov (United States)

    Seidelmann, Sara B; Vardeny, Orly; Claggett, Brian; Yu, Bing; Shah, Amil M; Ballantyne, Christie M; Selvin, Elizabeth; MacRae, Calum A; Boerwinkle, Eric; Solomon, Scott D

    2017-03-24

    Elevated B-type natriuretic peptide (BNP) levels are associated with heart failure and increased mortality in the general population. We investigated rs198389, a functional variant in the promoter region of the BNP gene ( NPPB ), in patients from the Atherosclerosis Risk in Communities Study to investigate associations with N-terminal pro-BNP (NT-proBNP) levels and outcomes. A total of 11 361 black and white patients with rs198389 genotyping attended visit 1 (aged 45-64 years; 1987-1989), with follow-up visits occurring every 3 years (visit 2-visit 4, 1990-1999), followed by visit 5 (2011-2013). NT-proBNP levels were measured at visits 2, 4, and 5. At visit 2, the GG genotype (frequency 18%) was associated with a 41% higher mean plasma level of NT-proBNP compared with the AA genotype (frequency 34%), with intermediate values observed in AGs ( P =4.2×10 -52 ). The GG genotype was associated with reduced systolic blood pressure (-1.6 mm Hg, P =0.006), diastolic blood pressure (-1 mm Hg, P =0.003), antihypertension medication use (odds ratio, 0.85; 95% CI, 0.74-0.97 [ P =0.02]), and hypertension (odds ratio, 0.81; 95% CI, 0.72-0.92 [ P =0.002]) compared with the AA genotype with intermediate values in AGs. These relationships persisted throughout subsequent visits. After a median follow-up of 23 years, there were 4031 deaths. With and without covariate adjustment, the GG genotype was associated with modestly lower mortality (hazard ratio, 0.86; 95% CI, 0.78-0.95), primarily reflective of cardiovascular death (hazard ratio, 0.75; 95% CI, 0.61-0.92), and increased residual lifespan of 8 months from 50 years of age ( P =0.02) versus AAs. The rs198389 G allele in the NPPB promoter is associated with elevated levels of NT-proBNP throughout adult life, reduced blood pressure, hypertension and cardiovascular mortality, and increased lifespan. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. An increase in the number of admitted patients with exercise-induced rhabdomyolysis.

    Science.gov (United States)

    Aalborg, Christian; Rød-Larsen, Cecilie; Leiro, Ingjerd; Aasebø, Willy

    2016-10-01

    Rhabdomyolysis may lead to serious complications, and treatment is both time-consuming and costly. The condition can be caused by many factors, including intense exercise. The purpose of this study was to investigate whether the number of hospitalisations due to exercise-induced rhabdomyolysis has changed in recent years. We describe the disease course in hospitalised patients, and compare disease course in individuals with exercise-induced rhabdomyolysis and rhabdomyolysis due to other causes. The study is a systematic review of medical records from Akershus University Hospital for the years 2008 and 2011 – 14. All hospitalised patients with diagnostic codes M62.8, M62.9 and T79.6 and creatine kinase levels > 5 000 IU/l were included. The cause of the rhabdomyolysis was recorded in addition to patient characteristics and the results of various laboratory tests. Of 161 patients who were hospitalised with rhabdomyolysis during the study period, 44 cases (27  %) were classified as exercise-induced. In 2008 there were no admissions due to exercise-induced rhabdomyolysis; in 2011 and 2012 there were six and four admissions respectively, while in 2014 there were 22. This gives an estimated incidence of 0.8/100 000 in 2012 and 4.6/100 000 in 2014. Strength-training was the cause of hospitalisation in 35 patients (80  % of the exercise-induced cases). Three patients (7  % of the exercise-induced cases) had transient stage 1 kidney injury, but there were no cases with stage 2 or stage 3 injury. By comparison, 52  % of patients with rhabdomyolysis due to another cause had kidney injury, of which 28  % was stage 2 or 3. The number of persons hospitalised with exercise-induced rhabdomyolysis has increased four-fold from 2011 to 2014, possibly due to changes in exercise habits in the population. None of the patients with exercise-induced rhabdomyolysis had serological signs of kidney injury upon hospital discharge.

  11. Differential isotope dansylation labeling combined with liquid chromatography mass spectrometry for quantification of intact and N-terminal truncated proteins

    International Nuclear Information System (INIS)

    Tang, Yanan; Li, Liang

    2013-01-01

    Graphical abstract: -- Highlights: •LC–MS was developed for quantifying protein mixtures containing both intact and N-terminal truncated proteins. • 12 C 2 -Dansylation of the N-terminal amino acid of proteins was done first, followed by microwave-assisted acid hydrolysis. •The released 12 C 2 -dansyl labeled N-terminal amino acid was quantified using 13 C 2 -dansyl labeled amino acid standards. •The method provided accurate and precise results for quantifying intact and N-terminal truncated proteins within 8 h. -- Abstract: The N-terminal amino acids of proteins are important structure units for maintaining the biological function, localization, and interaction networks of proteins. Under different biological conditions, one or several N-terminal amino acids could be cleaved from an intact protein due to processes, such as proteolysis, resulting in the change of protein properties. Thus, the ability to quantify the N-terminal truncated forms of proteins is of great importance, particularly in the area of development and production of protein-based drugs where the relative quantity of the intact protein and its truncated form needs to be monitored. In this work, we describe a rapid method for absolute quantification of protein mixtures containing intact and N-terminal truncated proteins. This method is based on dansylation labeling of the N-terminal amino acids of proteins, followed by microwave-assisted acid hydrolysis of the proteins into amino acids. It is shown that dansyl labeled amino acids are stable in acidic conditions and can be quantified by liquid chromatography mass spectrometry (LC–MS) with the use of isotope analog standards

  12. Correlation between arterial wall stiffness, N-terminal prohormone of brain natriuretic peptide, functional and structural myocardial abnormalities in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy

    Directory of Open Access Journals (Sweden)

    Viktoriya Aleksandrovna Serhiyenko

    2013-12-01

    Full Text Available Aim. To assess arterial wall stiffness, plasma levels of of N-terminal prohormone of brain natriuretic peptide (NT-proBNP, as well as functional state and structure of the myocardium in patients with type 2 diabetes mellitus (T2DM and cardiac autonomic neuropathy (CAN.Materials and Methods. The study involved a total of 65 patients with T2DM. 12 had no evidence of cardiovascular disease (CVD or CAN, 14 were diagnosed with subclinical stage of CAN, 18 – with functional stage, and 21 – with organic stage. We measured aortic pulse wave velocity (PWV, aortic augmentation index (AIx, brachial artery AIx, ambulatory arterial stiffness index (AASI and plasma levels of NT-proBNP. Clinical examination included ECG, Holter monitoring, ambulatory BP measurement and echocardiography.Results. Patients with isolated T2DM showed a trend for increased vascular wall stiffness. PWV was increased in patients with subclinical stage of CAN. Aortic and brachial AIx, PWV and AASI were elevated in patients with functional stage of CAN, PWV being significantly higher vs. subclinical CAN subgroup. Organic stage was characterized by pathologically increased values of all primary parameters; PWV and AASI were significantly higher compared with other groups. Development and progression of CAN was accompanied by an increase in NT-proBNP plasma levels. Concentration of NT-proBNP was in direct correlation with left ventricular mass (LVM and PWV. PWV and LVM values also directly correlated between themselves.Conclusion. Development and progression of CAN in patients with T2DM is accompanied by an increase in vascular wall stiffness. The elevation of plasma NT-proBNP in patients with T2DM correlates with the development of CAN and is significantly and independently associated with an increase in LVM and PWV. Our data suggests the pathophysiological interconnection between metabolic, functional and structural myocardial abnormalities in patients with T2DM and CAN.

  13. 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.

  14. Diagnostic value of exercise-induced changes in circulating high sensitive troponin T in stable chest pain patients

    DEFF Research Database (Denmark)

    Mouridsen, Mette Rauhe; Nielsen, Olav Wendelboe; Pedersen, Ole Dyg

    2013-01-01

    We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects.......We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects....

  15. Elevated Level of Troponin but Not N-Terminal Probrain Natriuretic Peptide Is Associated with Increased Risk of Sudden Cardiac Death in Hypertrophic Cardiomyopathy Calculated According to the ESC Guidelines 2014

    Directory of Open Access Journals (Sweden)

    Renata Rajtar-Salwa

    2017-01-01

    Full Text Available The aim of this study was to assess the relationship between biomarkers (high-sensitive troponin I [hs-TnI], N-Terminal probrain natriuretic peptide [NT-proBNP] and calculated 5-year percentage risk score of sudden cardiac death (SCD in hypertrophic cardiomyopathy (HCM. Methods. In 46 HCM patients (mean age 39 ± 7 years, 24 males and 22 females, echocardiographic examination, including the stimulating maneuvers to provoke maximized LVOT gradient, had been performed and next ECG Holter was immediately started. After 24 hours, the ECG Holter was finished and the hs-TnI and NT-proBNP have been measured. Patients were divided according to 1/value of both biomarkers (hs-TnI-positive and hs-TnI-negative subgroups and 2/(NT-proBNP lower and higher subgroup divided by median. Results. In comparison between 19 patients (hs-TnI positive versus 27 patients (hs-TnI negative, the calculated 5-year percentage risk of SCD in HCM was significantly greater (6.38 ± 4.17% versus 3.81 ± 3.23%, P0.05. Conclusions. Patients with HCM and positive hs-TnI test have a higher risk of SCD estimated according to SCD calculator recommended by the ESC Guidelines 2014 than patients with negative hs-TnI test.

  16. Serum levels of N-terminal-pro B-type natriuretic peptide as a diagnostic marker for left ventricular dysfunction in children with end-stage renal disease on hemodialysis.

    Science.gov (United States)

    Zoair, Amr Mohamed; Abdel-Hafez, Maher Ahmed; Mawlana, Wegdan; Sweylam, Mohamed Abdel-Rahman

    2016-01-01

    The objective of this study was to determine the diagnostic cutoff value of N-terminal-pro B-type natriuretic peptide (NT-pro BNP) as a marker of left ventricular (LV) dysfunction in children with end-stage renal disease (ESRD) on regular hemodialysis (HD). The study was carried out on thirty children with ESRD on regular HD and thirty healthy controls. Echocardiographic studies were done, including a conventional mode for ejection fraction, fractional shortening, tissue Doppler imaging, and longitudinal global strain by speckle tracking. Serum levels of NT-pro BNP were measured in venous blood samples before and about 30 min after HD by ELISA. Volume status was assessed by calculating interdialytic weight gain %. There were significant higher serum NT-pro BNP levels before HD (mean: 702.3 ± 274.3 ng/L) compared to controls (mean: 365.55 ± 76.5 ng/L) (P children with ESRD on regular HD. A postdialysis cutoff value of 630 ng/L could serve as a biochemical marker of LV dysfunction in those children regardless of chronic fluid overload.

  17. Exercise-induced maximum metabolic rate scaled to body mass by ...

    African Journals Online (AJOL)

    user

    2016-10-27

    Oct 27, 2016 ... while exercise-induced MMR is shown here to scale according to distribution network fractal dimensions. Hence, with a possibly obvious surface area explanatory cause, cold exposed MMR is left aside for present purposes. Initially developed for water flow description in river basins, network scaling laws ...

  18. Influence of artistic gymnastics on iron nutritional status and exercise-induced hemolysis in female athletes.

    Science.gov (United States)

    Sureira, Thaiz Mattos; Amancio, Olga Silverio; Pellegrini Braga, Josefina Aparecida

    2012-08-01

    This study evaluates the relationship between body iron losses and gains in artistic gymnastics female athletes. It shows that despite the low iron intake and exercise-induced hemolysis, iron deficiency or iron-deficiency anemia does not occur, but partial changes in the hematological profile do. The hypothesis that gymnasts' nutritional behavior contributes to anemia, which may be aggravated by exercise-induced hemolysis, led to this cross-sectional study, conducted with 43 female artistic gymnasts 6-16 yr old. The control group was formed by 40 nontraining girls, paired by age. Hemogram, serum iron, ferritin, soluble transferrin receptor, haptoglobin, total and fractional bilirubin, Type I urine, and parasitologic and occult fecal blood tests were evaluated. The athletes presented mean hematimetric and serum iron values (p = .020) higher than those of the control group. The bilirubin result discarded any hemolytic alteration in both groups. The haptoglobin results were lower in the athlete group (p = .002), confirming the incidence of exercise-induced hemolysis. Both groups presented low iron intake. The results suggest that artistic gymnastics practice leads to exercise-induced hemolysis and partially changes the hematological profile, although not causing iron deficiency or iron-deficiency anemia, even in the presence of low iron intake.

  19. Adaptation of exercise-induced stress in well-trained healthy young men

    NARCIS (Netherlands)

    Janssen Duijghuijsen, L.M.; Keijer, J.; Mensink, M.R.; Lenaerts, Kaatje; Ridder, L.O.; Nierkens, Stefan; Kartaram, Shirley; Verschuren, Martie C.M.; Pieters, Raymond; Bas, Richard; Witkamp, R.F.; Wichers, H.J.; Norren, van K.

    2017-01-01

    Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com) we determined the test-retest repeatability in responses to exercise in well-trained individuals.
    Eleven

  20. Exercise-induced laryngeal obstructions: prevalence and symptoms in the general public

    DEFF Research Database (Denmark)

    Christensen, Pernille Melia; Thomsen, S F; Rasmussen, N

    2011-01-01

    Respiratory difficulties caused by exercise-induced laryngeal obstructions (EILOs) are reported with increasing frequency. The aim of this study was to assess the prevalence and symptoms of EILOs and their relation to airway hyperresponsiveness (AHR). In total, 556 randomly selected youths in Cop...

  1. Exercise Challenge for Exercise-Induced Bronchospasm. Confirming Presence, Evaluating Control.

    Science.gov (United States)

    Kaplan, Ted A.

    1995-01-01

    Exercise-induced bronchospasm commonly strikes young people, keeping many away from activity. The exercise challenge test (a powerful tool in diagnosing the condition, fine-tuning treatment, and improving patient compliance) can help get patients back in action. Knowing how to interpret and use test results helps physicians expedite effective…

  2. Effects of Dietary Induced Weight Loss on Exercise-Induced Bronchoconstriction in Overweight and Obese Children

    NARCIS (Netherlands)

    van Leeuwen, Janneke C.; Hoogstrate, Mira; Duiverman, Eric J.; Thio, Boony J.

    2014-01-01

    RationalePrevious studies showed that obesity in asthmatic children is associated with more severe exercise-induced bronchoconstriction (EIB), compared with non-obese asthmatic children. This study investigates the effect of weight loss on EIB in overweight and obese asthmatic children. MethodsIn

  3. Exercise-induced asthma in a group of South African schoolchildren ...

    African Journals Online (AJOL)

    Objectives. The study was conducted to ascertain whether physical education teachers, using a peak flow meter, could reliably screen for exercise-induced asthma (EIA) in children during free running. Design, setting and subjects. The study was conducted using a convenience sample of male pupils between the ages of 12 ...

  4. Exercise-induced maximum metabolic rate scaled to body mass by ...

    African Journals Online (AJOL)

    The central postulation of the present approach to metabolic rate scaling is that exercise-induced maximum aerobic metabolic rate (MMR) is proportional to the fractal extent (V) of an animal. Total fractal extent can be calculated from the sum of the fractal extents of the capillary service units, as specified by the formula V ...

  5. Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest

    DEFF Research Database (Denmark)

    Kiilerich, Kristian; Jørgensen, Stine Ringholm; Biensø, Rasmus Sjørup

    2011-01-01

    To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), 6 healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an OGTT and a one-legged knee...

  6. Protective effect of a low single dose inhaled steroid against exercise induced bronchoconstriction

    NARCIS (Netherlands)

    Visser, R.; Wind, M.; de Graaf, B.; de Jongh, Franciscus H.C.; van der Palen, Jacobus Adrianus Maria; Thio, B.J.

    2015-01-01

    Objective Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against

  7. Food-Dependent Exercise-Induced Anaphylaxis - Kasuistik med hydrolyseret valleprotein

    DEFF Research Database (Denmark)

    Junker Christensen, Morten

    2013-01-01

    Formål / Introduktion: Patienter med Food-Dependent Exercise-Induced Anaphylaxis (FDEIA) eller løbershock kan udvikle livstruende allergiske reaktioner (anafylaksi), når de kombinere fysisk anstrengelse med samtidig indtagelse af et normalt tolereret fødeemne - oftest hvede. Hydrolysering af prot...

  8. Exercise-induced laryngeal obstructions: prevalence and symptoms in the general public

    DEFF Research Database (Denmark)

    Christensen, Pernille Melia; Thomsen, S F; Rasmussen, N

    2011-01-01

    Respiratory difficulties caused by exercise-induced laryngeal obstructions (EILOs) are reported with increasing frequency. The aim of this study was to assess the prevalence and symptoms of EILOs and their relation to airway hyperresponsiveness (AHR). In total, 556 randomly selected youths...

  9. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    DEFF Research Database (Denmark)

    Seifert, Thomas; Fisher, James P; Young, Colin N

    2010-01-01

    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebr...

  10. Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma

    DEFF Research Database (Denmark)

    Duong, MyLinh; Subbarao, Padmaja; Adelroth, Ellinor

    2008-01-01

    BACKGROUND: The relationship between eosinophilic airway inflammation and exercise-induced bronchoconstriction (EIB), and the response to inhaled corticosteroid (ICS) therapy was examined. METHODS: Twenty-six steroid-naïve asthmatic patients with EIB were randomized to two parallel, double-blind,...

  11. Green Tea Catechin Consumption Enhances Exercise-Induced Abdominal Fat Loss

    Science.gov (United States)

    Aim: This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercised-induced weight loss. Methods: Participants (N=132) were randomly assigned to receive a 500 mL beverage containing approximately 625 mg of...

  12. Adaptation of exercise-induced stress in well-trained healthy young men

    NARCIS (Netherlands)

    JanssenDuijghuijsen, Lonneke M; Keijer, Jaap; Mensink, Marco; Lenaerts, Kaatje; Ridder, Lars; Nierkens, Stefan; Kartaram, Shirley W; Verschuren, Martie C M; Pieters, Raymond H H; Bas, Richard; Witkamp, Renger F; Wichers, Harry J; van Norren, Klaske

    2017-01-01

    Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com) we determined the test-retest repeatability in responses to exercise in well-trained individuals. Eleven

  13. Role of Leukotriene Receptor Antagonists in the Treatment of Exercise-Induced Bronchoconstriction: A Review

    Directory of Open Access Journals (Sweden)

    Philteos George S

    2005-06-01

    Full Text Available Abstract Asthma is a very common disorder that still causes significant morbidity and mortality. A high percentage of individuals with asthma also experience exercise-induced bronchoconstriction (EIB. This article reviews the current literature and updates the reader on the safety, efficacy, and clinical applications of leukotriene modifiers in the treatment of EIB.

  14. Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children

    NARCIS (Netherlands)

    Kersten, Elin T. G.; van Leeuwen, Janneke C.; Brand, Paul L. P.; Duiverman, Eric J.; de Jongh, Frans H. C.; Thio, Bernard J.; Driessen, Jean M. M.

    Rationale Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children. Methods: This was a double-blind,

  15. Update on Exercise-Induced Asthma. A Report of the Olympic Exercise Asthma Summit Conference.

    Science.gov (United States)

    Storms, William W.; Joyner, David M.

    1997-01-01

    Summarizes results from the Olympic Exercise Asthma Summit Conference, offering the latest on identifying and managing exercise-induced asthma (EIA). Concludes that effective pharmacologic and nonpharmacologic treatment is available, but EIA is underrecognized and underdiagnosed. Physicians should look for it in all patients, including school…

  16. Can flow-volume loops be used to diagnose exercise induced laryngeal obstructions?

    DEFF Research Database (Denmark)

    Christensen, Pernille M; Maltbæk, Niels; Jørgensen, Inger M

    2013-01-01

    BACKGROUND: Pre- and post-exercise flow-volume loops are often recommended as an easy non-invasive method for diagnosing or excluding exercise-induced laryngeal obstructions in patients with exercise-related respiratory symptoms. However, at present there is no evidence for this recommendation. A...

  17. Coronary arteriography and left ventriculography during spontaneous and exercise-induced ST segment elevation in patients with variant angina

    International Nuclear Information System (INIS)

    Matsuda, Y.; Ozaki, M.; Ogawa, H.; Naito, H.; Yoshino, F.; Katayama, K.; Fujii, T.; Matsuzaki, M.; Kusukawa, R.

    1983-01-01

    The present study is an angiographic demonstration of coronary artery spasm during both spontaneous and exercise-induced angina in three patients with variant angina. In each case, clinical, ECG, coronary angiographic, and left ventriculographic observations were made at rest, during spontaneous angina, and during exercise-induced angina. The character of chest pain was similar during spontaneous and exercise-induced episodes. ST segment elevation was present in the anterior ECG leads during both episodes. The left anterior descending coronary artery became partially or totally obstructed during both types of attacks. When coronary spasm was demonstrated during both types of attacks, left ventriculography disclosed akinetic or dyskinetic wall motion in the area supplied by the involved artery. In those patients with reproducible exercise-induced ST segment elevation and chest pain, thallium-201 scintigraphy showed areas of reversible anteroseptal hypoperfusion. Thus in selected patients exercise-induced attacks of angina were similar to spontaneous episodes

  18. Exercise-Induced Secretion of FGF21 and Follistatin Are Blocked by Pancreatic Clamp and Impaired in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Hansen, Jakob Schiøler; Pedersen, Bente Klarlund; Xu, Guowang

    2016-01-01

    of the study was to investigate the regulatory roles of glucagon to insulin ratio and T2D on exercise-induced FGF21 and follistatin secretion. Design /Interventions: Young healthy males performed a 2-hour bicycle exercise bout followed by 5 hours of rest in supine position with and without a pancreatic clamp...... a 10-fold (P clamp. Exercise with the pancreatic clamp completely blunted the exercise-induced increase in FGF21 (P = .007), whereas the induction of follistatin was approximately 50% reduced (P...... = .04). Exercise-induced FGF21 secretion was completely absent in patients with T2D, whereas the exercise-induced follistatin increase was impaired. CONCLUSIONS/INTERPRETATION: Exercise-induced increases in plasma FGF21 and follistatin are attenuated by the pancreatic clamp, indicating important roles...

  19. N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Boesen, Mikael; Olsen, Michael

    2004-01-01

    , while patients with either high NT-proBNP or CV disease had a three-four-fold increased risk. In conclusion NT-proBNP predicts LV mass in hypertensive patients and is a very strong prognostic marker in these patients. This could indicate a use of NT-proBNP in the future for risk stratification...

  20. Miro's N-Terminal GTPase Domain Is Required for Transport of Mitochondria into Axons and Dendrites

    Science.gov (United States)

    Babic, Milos; Russo, Gary J.; Wellington, Andrea J.; Sangston, Ryan M.; Gonzalez, Migdalia

    2015-01-01

    Mitochondria are dynamically transported in and out of neuronal processes to maintain neuronal excitability and synaptic function. In higher eukaryotes, the mitochondrial GTPase Miro binds Milton/TRAK adaptor proteins linking microtubule motors to mitochondria. Here we show that Drosophila Miro (dMiro), which has previously been shown to be required for kinesin-driven axonal transport, is also critically required for the dynein-driven distribution of mitochondria into dendrites. In addition, we used the loss-of-function mutations dMiroT25N and dMiroT460N to determine the significance of dMiro's N-terminal and C-terminal GTPase domains, respectively. Expression of dMiroT25N in the absence of endogenous dMiro caused premature lethality and arrested development at a pupal stage. dMiroT25N accumulated mitochondria in the soma of larval motor and sensory neurons, and prevented their kinesin-dependent and dynein-dependent distribution into axons and dendrites, respectively. dMiroT25N mutant mitochondria also were severely fragmented and exhibited reduced kinesin and dynein motility in axons. In contrast, dMiroT460N did not impair viability, mitochondrial size, or the distribution of mitochondria. However, dMiroT460N reduced dynein motility during retrograde mitochondrial transport in axons. Finally, we show that substitutions analogous to the constitutively active Ras-G12V mutation in dMiro's N-terminal and C-terminal GTPase domains cause neomorphic phenotypic effects that are likely unrelated to the normal function of each GTPase domain. Overall, our analysis indicates that dMiro's N-terminal GTPase domain is critically required for viability, mitochondrial size, and the distribution of mitochondria out of the neuronal soma regardless of the employed motor, likely by promoting the transition from a stationary to a motile state. PMID:25855186

  1. Aldehyde stress-mediated novel modification of proteins: epimerization of the N-terminal amino acid.

    Science.gov (United States)

    Kajita, Ryo; Goto, Takaaki; Lee, Seon Hwa; Oe, Tomoyuki

    2013-12-16

    Various kinds of aldehyde-mediated chemical modifications of proteins have been identified as being exclusively covalent. We report a unique noncovalent modification: the aldehyde-mediated epimerization of the N-terminal amino acid. Epimerization of amino acids is thought to cause conformational changes that alter their biological activity. However, few mechanistic studies have been performed, because epimerization of an amino acid is a miniscule change in a whole protein. Furthermore, it does not produce a mass shift, making mass spectrometric analysis difficult. Here, we have demonstrated epimerization mediated by endogenous aldehydes. A model peptide, with an N-terminal l- or d-FMRFamide, was incubated with an endogenous or synthetic aldehyde [acetaldehyde, methylglyoxal, pyridoxal 5'-phosphate (PLP), 4-oxo-2(E)-nonenal, 4-hydroxy-2(E)-nonenal, d-glucose (Glc), 4- or 2-pyridinecarboxaldehyde] under physiological conditions. Each reaction mixture was analyzed by liquid chromatography with ultraviolet detection and/or electrospray ionization mass spectrometry. Considerable epimerization occurred after incubation with some endogenous aldehydes (PLP, 40.6% after 1 day; Glc with copper ions, 6.5% after 7 days). Moreover, the epimerization also occurred in whole proteins (human serum albumin and PLP, 26.3% after 1 day). Tandem mass spectrometric studies, including deuterium labeling and sodium borohydride reduction, suggested that the epimerization results from initial Schiff base formation followed by tautomerization to ketimine that causes the chirality to be lost. This suggests that the epimerization of the N-terminal amino acid can also occur in vivo as a post-translational modification under a high level of aldehyde stress.

  2. KV4.3 N-terminal deletion mutant Δ2–39

    Science.gov (United States)

    Hovind, Laura J; Skerritt, Matthew R

    2011-01-01

    Gating transitions in the KV4.3 N-terminal deletion mutant Δ2–39 were characterized in the absence and presence of KChIP2b. We particularly focused on gating characteristics of macroscopic (open state) versus closed state inactivation (CSI) and recovery. In the absence of KChIP2b Δ2–39 did not significantly alter the steady-state activation “a4” relationship or general CSI characteristics, but it did slow the kinetics of deactivation, macroscopic inactivation and macroscopic recovery. Recovery kinetics (for both WT KV4.3 and Δ2–39) were complicated and displayed sigmoidicity, a process which was enhanced by Δ2–39. Deletion of the proximal N-terminal domain therefore appeared to specifically slow mechanisms involved in regulating gating transitions occurring after the channel open state(s) had been reached. In the presence of KChIP2b Δ2–39 recovery kinetics (from both macroscopic and CSI) were accelerated, with an apparent reduction in initial sigmoidicity. Hyperpolarizing shifts in both “a4” and isochronal inactivation “i” were also produced. KChIP2b-mediated remodeling of KV4.3 gating transitions was therefore not obligatorily dependent upon an intact N-terminus. To account for these effects we propose that KChIP2 regulatory domains exist in KV4.3 α subunit regions outside of the proximal N-terminal. In addition to regulating macroscopic inactivation, we also propose that the KV4.3 N-terminus may act as a novel regulator of deactivation-recovery coupling. PMID:21057209

  3. Asymmetric configurations and N-terminal rearrangements in connexin26 gap junction channels.

    Science.gov (United States)

    Oshima, Atsunori; Tani, Kazutoshi; Toloue, Masoud M; Hiroaki, Yoko; Smock, Amy; Inukai, Sayaka; Cone, Angela; Nicholson, Bruce J; Sosinsky, Gina E; Fujiyoshi, Yoshinori

    2011-01-21

    Gap junction channels are unique in that they possess multiple mechanisms for channel closure, several of which involve the N terminus as a key component in gating, and possibly assembly. Here, we present electron crystallographic structures of a mutant human connexin26 (Cx26M34A) and an N-terminal deletion of this mutant (Cx26M34Adel2-7) at 6-Å and 10-Å resolutions, respectively. The three-dimensional map of Cx26M34A was improved by data from 60° tilt images and revealed a breakdown of the hexagonal symmetry in a connexin hemichannel, particularly in the cytoplasmic domain regions at the ends of the transmembrane helices. The Cx26M34A structure contained an asymmetric density in the channel vestibule ("plug") that was decreased in the Cx26M34Adel2-7 structure, indicating that the N terminus significantly contributes to form this plug feature. Functional analysis of the Cx26M34A channels revealed that these channels are predominantly closed, with the residual electrical conductance showing normal voltage gating. N-terminal deletion mutants with and without the M34A mutation showed no electrical activity in paired Xenopus oocytes and significantly decreased dye permeability in HeLa cells. Comparing this closed structure with the recently published X-ray structure of wild-type Cx26, which is proposed to be in an open state, revealed a radial outward shift in the transmembrane helices in the closed state, presumably to accommodate the N-terminal plug occluding the pore. Because both Cx26del2-7 and Cx26M34Adel2-7 channels are closed, the N terminus appears to have a prominent role in stabilizing the open configuration. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Peptidase family U34 belongs to the superfamily of N-terminal nucleophile hydrolases

    Science.gov (United States)

    Pei, Jimin; Grishin, Nick V.

    2003-01-01

    Peptidase family U34 consists of enzymes with unclear catalytic mechanism, for instance, dipeptidase A from Lactobacillus helveticus. Using extensive sequence similarity searches, we infer that U34 family members are homologous to penicillin V acylases (PVA) and thus potentially adopt the N-terminal nucleophile (Ntn) hydrolase fold. Comparative sequence and structural analysis reveals a cysteine as the catalytic nucleophile as well as other conserved residues important for catalysis. The PVA/U34 family is variable in sequence and exhibits great diversity in substrate specificity, to include enzymes such as choloyglycine hydrolases, acid ceramidases, isopenicillin N acyltransferases, and a subgroup of eukaryotic proteins with unclear function. PMID:12717035

  5. Clostridium botulinum strains producing BoNT/F4 or BoNT/F5.

    Science.gov (United States)

    Raphael, Brian H; Bradshaw, Marite; Kalb, Suzanne R; Joseph, Lavin A; Lúquez, Carolina; Barr, John R; Johnson, Eric A; Maslanka, Susan E

    2014-05-01

    Botulinum neurotoxin type F (BoNT/F) may be produced by Clostridium botulinum alone or in combination with another toxin type such as BoNT/A or BoNT/B. Type F neurotoxin gene sequences have been further classified into seven toxin subtypes. Recently, the genome sequence of one strain of C. botulinum (Af84) was shown to contain three neurotoxin genes (bont/F4, bont/F5, and bont/A2). In this study, eight strains containing bont/F4 and seven strains containing bont/F5 were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis, allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containing bont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboring bont/F5. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring either bont/F4 or bont/F5 are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously, suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of a bont/F5-carrying plasmid among strains of diverse genomic backgrounds.

  6. Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline

    Directory of Open Access Journals (Sweden)

    Christelle Folio

    2017-11-01

    Full Text Available Feline immunodeficiency virus (FIV is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS in cats and wild felines. Its capsid protein (CA drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA.

  7. Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline.

    Science.gov (United States)

    Folio, Christelle; Sierra, Natalia; Dujardin, Marie; Alvarez, Guzman; Guillon, Christophe

    2017-11-09

    Feline immunodeficiency virus (FIV) is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS) in cats and wild felines. Its capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg-Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA.

  8. Predictive value of NT-proBNP for 30-day mortality in patients with non-ST-elevation acute coronary syndromes: a comparison with the GRACE and TIMI risk scores.

    Science.gov (United States)

    Schellings, Dirk Aam; Adiyaman, Ahmet; Dambrink, Jan-Henk E; Gosselink, At Marcel; Kedhi, Elvin; Roolvink, Vincent; Ottervanger, Jan Paul; Van't Hof, Arnoud Wj

    2016-01-01

    The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts outcome in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Whether NT-proBNP has incremental prognostic value beyond established risk strategies is still questionable. To evaluate the predictive value of NT-proBNP for 30-day mortality over and beyond the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) risk scores in patients with NSTE-ACS. Patients included in our ACS registry were candidates. NT-proBNP levels on admission were measured and the GRACE and TIMI risk scores were assessed. We compared the predictive value of NT-proBNP to both risk scores and evaluated whether NT-proBNP improves prognostication by using receiver operator curves and measures of discrimination improvement. A total of 1324 patients were included and 50 patients died during follow-up. On logistic regression analysis NT-proBNP and the GRACE risk score (but not the TIMI risk score) both independently predicted mortality at 30 days. The predictive value of NT-proBNP did not differ significantly compared to the GRACE risk score (area under the curve [AUC]) 0.85 vs 0.87 p =0.67) but was considerably higher in comparison to the TIMI risk score (AUC 0.60 p risk score by adding NT-proBNP did not improve prognostication: AUC 0.86 ( p =0.57), integrated discrimination improvement 0.04 ( p =0.003), net reclassification improvement 0.12 ( p =0.21). In patients with NSTE-ACS, NT-proBNP and the GRACE risk score (but not the TIMI risk score) both have good and comparable predictive value for 30-day mortality. However, incremental prognostic value of NT-proBNP beyond the GRACE risk score could not be demonstrated.

  9. Improving Prediction of Postoperative Myocardial Infarction with High-Sensitivity Cardiac Troponin T and NT-proBNP

    Science.gov (United States)

    Kopec, Michael; Duma, Andreas; Helwani, Mohammad A.; Brown, Jamie; Brown, Frank; Gage, Brian F.; Gibson, David W.; Miller, J. Philip; Novak, Eric; Jaffe, Allan S.; Apple, Fred S.; Scott, Mitchell G.; Nagele, Peter

    2016-01-01

    Background This study sought to determine if preoperatively measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) improve cardiac risk prediction in patients undergoing major non-cardiac surgery when compared to standard risk indices. Methods In this ancillary study to the Vitamins in Nitrous Oxide (VINO) trial, patients were included who had preoperative hs-cTnT and NT-proBNP measured (n=572). Study outcome was the incidence of postoperative myocardial infarction (MI) within the first three postoperative days. hs-cTn was considered elevated if >14 ng/L and NT-proBNP if >300 ng/L. Additional cutoff values were investigated based on ROC statistics. Biomarker risk prediction was compared to Lee’s Revised Cardiac Risk Index (RCRI) using standard methods and net reclassification index (NRI). Results The addition of hs-cTnT (>14 ng/L) and NT-proBNP (>300 ng/L) to RCRI significantly improved the prediction of postoperative MI (event rate 30/572 (5.2%), AUC ROC increased from 0.590 to 0.716 with a 0.66 NRI [95% CI 0.32 – 0.99] p<0.001). Using 108 ng/L as cutoff for NT-proBNP improved sensitivity compared to 300 ng/L (0.87 vs. 0.53). Sensitivity, specificity, positive and negative predictive value for hs-cTnT were 0.70, 0.60, 0.09 and 0.97, and 0.53, 0.68, 0.08, 0.96 for NT-proBNP. Conclusions The addition of cardiac biomarkers hs-cTnT and NT-proBNP to RCRI improves prediction of adverse cardiac events in the immediate postoperative period after major non-cardiac surgery. The high negative predictive value of preoperative hs-cTnT and NT-proBNP suggest usefulness as a “rule-out” test to confirm low risk of postoperative MI. PMID:28002165

  10. Hypertension-Related Gene Polymorphisms of G-Protein-Coupled Receptor Kinase 4 Are Associated with NT-proBNP Concentration in Normotensive Healthy Adults

    Science.gov (United States)

    Yatabe, Junichi; Yatabe, Midori S.; Yoneda, Minoru; Felder, Robin A.; Jose, Pedro A.; Sanada, Hironobu

    2012-01-01

    G protein-coupled receptor kinase 4 (GRK4) with activating polymorphisms desensitize the natriuric renal tubular D1 dopamine receptor, and these GRK4 polymorphisms are strongly associated with salt sensitivity and hypertension. Meanwhile, N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in detecting slight volume expansion. However, relations between hypertension-related gene polymorphisms including GRK4 and cardiovascular indices such as NT-proBNP are not clear, especially in healthy subjects. Therefore, various hypertension-related polymorphisms and cardiovascular indices were analyzed in 97 normotensive, healthy Japanese adults. NT-proBNP levels were significantly higher in subjects with two or more GRK4 polymorphic alleles. Other hypertension-related gene polymorphisms, such as those of renin-angiotensin-aldosterone system genes, did not correlate with NT-proBNP. There was no significant association between any of the hypertension-related gene polymorphisms and central systolic blood pressure, cardioankle vascular index, augmentation index, plasma aldosterone concentration, or an oxidative stress marker, urinary 8-OHdG. Normotensive individuals with GRK4 polymorphisms show increased serum NT-proBNP concentration and may be at a greater risk of developing hypertension and cardiovascular disease. PMID:22518293

  11. Hypertension-Related Gene Polymorphisms of G-Protein-Coupled Receptor Kinase 4 Are Associated with NT-proBNP Concentration in Normotensive Healthy Adults

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    Junichi Yatabe

    2012-01-01

    Full Text Available G protein-coupled receptor kinase 4 (GRK4 with activating polymorphisms desensitize the natriuric renal tubular D1 dopamine receptor, and these GRK4 polymorphisms are strongly associated with salt sensitivity and hypertension. Meanwhile, N-terminal pro-B-type natriuretic peptide (NT-proBNP may be useful in detecting slight volume expansion. However, relations between hypertension-related gene polymorphisms including GRK4 and cardiovascular indices such as NT-proBNP are not clear, especially in healthy subjects. Therefore, various hypertension-related polymorphisms and cardiovascular indices were analyzed in 97 normotensive, healthy Japanese adults. NT-proBNP levels were significantly higher in subjects with two or more GRK4 polymorphic alleles. Other hypertension-related gene polymorphisms, such as those of renin-angiotensin-aldosterone system genes, did not correlate with NT-proBNP. There was no significant association between any of the hypertension-related gene polymorphisms and central systolic blood pressure, cardioankle vascular index, augmentation index, plasma aldosterone concentration, or an oxidative stress marker, urinary 8-OHdG. Normotensive individuals with GRK4 polymorphisms show increased serum NT-proBNP concentration and may be at a greater risk of developing hypertension and cardiovascular disease.

  12. Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease.

    Science.gov (United States)

    Eriksson, Anders S; Häggström, Jens; Pedersen, Henrik Duelund; Hansson, Kerstin; Järvinen, Anna-Kaisa; Haukka, Jari; Kvart, Clarence

    2014-09-01

    To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p 1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations ≤ 1000 pmol/l (p 130 beats per minute) and grade of murmur (≥ 3/6). The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding

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    Ye, Qiaozhen; Kim, Dong Hyun; Dereli, Ihsan; Rosenberg, Scott C.; Hagemann, Goetz; Herzog, Franz; Tóth, Attila; Cleveland, Don W.; Corbett, Kevin D.

    2017-06-28

    Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed “closure motifs”. The AAA+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain–closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31comet. We show that p31comet binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 “pore loops”, which then unfold MAD2 in the presence of ATP. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro, and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function. Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain–closure motif complexes by TRIP13.

  14. Novel Insights into Structure-Activity Relationships of N-Terminally Modified PACE4 Inhibitors.

    Science.gov (United States)

    Kwiatkowska, Anna; Couture, Frédéric; Levesque, Christine; Ly, Kévin; Beauchemin, Sophie; Desjardins, Roxane; Neugebauer, Witold; Dory, Yves L; Day, Robert

    2016-02-04

    PACE4 plays important roles in prostate cancer cell proliferation. The inhibition of this enzyme has been shown to slow prostate cancer progression and is emerging as a promising therapeutic strategy. In previous work, we developed a highly potent and selective PACE4 inhibitor, the multi-Leu (ML) peptide, an octapeptide with the sequence Ac-LLLLRVKR-NH2 . Here, with the objective of developing a useful compound for in vivo administration, we investigate the effect of N-terminal modifications. The inhibitory activity, toxicity, stability, and cell penetration properties of the resulting analogues were studied and compared to the unmodified inhibitor. Our results show that the incorporation of a polyethylene glycol (PEG) moiety leads to a loss of antiproliferative activity, whereas the attachment of a lipid chain preserves or improves it. However, the lipidated peptides are significantly more toxic when compared with their unmodified counterparts. Therefore, the best results were achieved not by the N-terminal extension but by the protection of both ends with the d-Leu residue and 4-amidinobenzylamide, which yielded the most stable inhibitor, with an excellent activity and toxicity profile. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The unique N-terminal zinc finger of synaptotagmin-like protein 4 reveals FYVE structure.

    Science.gov (United States)

    Miyamoto, Kazuhide; Nakatani, Arisa; Saito, Kazuki

    2017-12-01

    Synaptotagmin-like protein 4 (Slp4), expressed in human platelets, is associated with dense granule release. Slp4 is comprised of the N-terminal zinc finger, Slp homology domain, and C2 domains. We synthesized a compact construct (the Slp4N peptide) corresponding to the Slp4 N-terminal zinc finger. Herein, we have determined the solution structure of the Slp4N peptide by nuclear magnetic resonance (NMR). Furthermore, experimental, chemical modification of Cys residues revealed that the Slp4N peptide binds two zinc atoms to mediate proper folding. NMR data showed that eight Cys residues coordinate zinc atoms in a cross-brace fashion. The Simple Modular Architecture Research Tool database predicted the structure of Slp4N as a RING finger. However, the actual structure of the Slp4N peptide adopts a unique C 4 C 4 -type FYVE fold and is distinct from a RING fold. To create an artificial RING finger (ARF) with specific ubiquitin-conjugating enzyme (E2)-binding capability, cross-brace structures with eight zinc-ligating residues are needed as the scaffold. The cross-brace structure of the Slp4N peptide could be utilized as the scaffold for the design of ARFs. © 2017 The Protein Society.

  16. In Silico Identification and Characterization of N-Terminal Acetyltransferase Genes of Poplar (Populus trichocarpa

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    Hang-Yong Zhu

    2014-01-01

    Full Text Available N-terminal acetyltransferase (Nats complex is responsible for protein N-terminal acetylation (Nα-acetylation, which is one of the most common covalent modifications of eukaryotic proteins. Although genome-wide investigation and characterization of Nat catalytic subunits (CS and auxiliary subunits (AS have been conducted in yeast and humans they remain unexplored in plants. Here we report on the identification of eleven genes encoding eleven putative Nat CS polypeptides, and five genes encoding five putative Nat AS polypeptides in Populus. We document that the expansion of Nat CS genes occurs as duplicated blocks distributed across 10 of the 19 poplar chromosomes, likely only as a result of segmental duplication events. Based on phylogenetic analysis, poplar Nat CS were assigned to six subgroups, which corresponded well to the Nat CS types (CS of Nat A–F, being consistent with previous reports in humans and yeast. In silico analysis of microarray data showed that in the process of normal development of the poplar, their Nat CS and AS genes are commonly expressed at one relatively low level but share distinct tissue-specific expression patterns. This exhaustive survey of Nat genes in poplar provides important information to assist future studies on their functional role in poplar.

  17. Specificity of N-terminal methionyl peptidase: analysis by site-directed mutagenesis

    International Nuclear Information System (INIS)

    Kasper, T.J.; Boissel, J.P.; Bunn, H.F.

    1987-01-01

    The start site of eukaryotic translation is normally an AUG codon. The corresponding N-terminal methionine is most often removed when the nascent chain reaches about 30 residues. Data from a survey of 1764 eukaryotic protein sequences suggest that the residue adjacent to the initiator Met determines Met cleavage. In order to investigate the mechanism of this reaction, the authors have prepared oligonucleotide-directed mutants of human β-globin from gapped heteroduplexes of a T3/T7 plasmid containing a globin cDNA clone. To date, the authors have produced mutants encoding for 15 of 19 possible amino acid replacements at position 1 in the β-globin chain. These mutants have been confirmed by dideoxy sequencing, transcribed in vitro, and translated in a rabbit reticulocyte lysate in the presence of 35 S-methionine. Labeled translation products were then isolated by cation exchange HPLC, and tryptic peptides were analyzed by RP-HPLC. Thus far, this structural analysis has shown that for β-1 Val, Ala, and Ser, the initiator Met is cleaved, whereas for β-1 Lys, Met, Glu, Trp, Asn, Tyr, and Glu, initiator Met is retained. For β-1 Leu initiator Met is cleaved with a frequency of about 50%. These results are consistent with the data obtained from the previous survey. The expression of site-directed mutants in a cell-free system can also be used to investigate other N-terminal processing events, such as acetylation and myristylation

  18. The N-terminal domain of apolipoprotein B-100: structural characterization by homology modeling

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    Khachfe Hassan M

    2007-07-01

    Full Text Available Abstract Background Apolipoprotein B-100 (apo B-100 stands as one of the largest proteins in humans. Its large size of 4536 amino acids hampers the production of X-ray diffraction quality crystals and hinders in-solution NMR analysis, and thus necessitates a domain-based approach for the structural characterization of the multi-domain full-length apo B. Results The structure of apo B-17 (the N-terminal 17% of apolipoprotein B-100 was predicted by homology modeling based on the structure of the N-terminal domain of lipovitellin (LV, a protein that shares not only sequence similarity with B17, but also a functional aspect of lipid binding and transport. The model structure was first induced to accommodate the six disulfide bonds found in that region, and then optimized using simulated annealing. Conclusion The content of secondary structural elements in this model structure correlates well with the reported data from other biophysical probes. The overall topology of the model conforms with the structural outline corresponding to the apo B-17 domain as seen in the EM representation of the complete LDL structure.

  19. Molecular cloning and biologically active production of IpaD N-terminal region.

    Science.gov (United States)

    Hesaraki, Mahdi; Saadati, Mojtaba; Honari, Hossein; Olad, Gholamreza; Heiat, Mohammad; Malaei, Fatemeh; Ranjbar, Reza

    2013-07-01

    Shigella is known as pathogenic intestinal bacteria in high dispersion and pathogenic bacteria due to invasive plasmid antigen (Ipa). So far, a number of Ipa proteins have been studied to introduce a new candidate vaccine. Here, for the first time, we examined whether the N-terminal region of IpaD(72-162) could be a proper candidate for Shigella vaccine. Initially, the DNA sequence coding N-terminal region was isolated by PCR from Shigella dysenteriae type I and cloned into pET-28a expression vector. Then, the heterologous protein was expressed, optimized and purified by affinity Ni-NTA column. Western blot analysis using, His-tag and IpaD(72-162) polyclonal antibodies, confirmed the purity and specificity of the recombinant protein, respectively. Subsequently, the high immunogenicity of the antigen was shown by ELISA. The results of the sereny test in Guinea pigs showed that IpaD(72-162) provides a protective system against Shigella flexneri 5a and S. dysenteriae type I. Copyright © 2013. Published by Elsevier Ltd.

  20. Isolation and N-terminal sequencing of a novel cadmium-binding protein from Boletus edulis

    Science.gov (United States)

    Collin-Hansen, C.; Andersen, R. A.; Steinnes, E.

    2003-05-01

    A Cd-binding protein was isolated from the popular edible mushroom Boletus edulis, which is a hyperaccumulator of both Cd and Hg. Wild-growing samples of B. edulis were collected from soils rich in Cd. Cd radiotracer was added to the crude protein preparation obtained from ethanol precipitation of heat-treated cytosol. Proteins were then further separated in two consecutive steps; gel filtration and anion exchange chromatography. In both steps the Cd radiotracer profile showed only one distinct peak, which corresponded well with the profiles of endogenous Cd obtained by atomic absorption spectrophotometry (AAS). Concentrations of the essential elements Cu and Zn were low in the protein fractions high in Cd. N-terminal sequencing performed on the Cd-binding protein fractions revealed a protein with a novel amino acid sequence, which contained aromatic amino acids as well as proline. Both the N-terminal sequencing and spectrofluorimetric analysis with EDTA and ABD-F (4-aminosulfonyl-7-fluoro-2, 1, 3-benzoxadiazole) failed to detect cysteine in the Cd-binding fractions. These findings conclude that the novel protein does not belong to the metallothionein family. The results suggest a role for the protein in Cd transport and storage, and they are of importance in view of toxicology and food chemistry, but also for environmental protection.

  1. UV laser-induced histone-DNA crosslinking proceeds via the N-terminal tails

    International Nuclear Information System (INIS)

    Stefanovski, V.; Dimitrov, S.; Angelov, D.; Keskinova, E.; Pashev, I.

    1990-01-01

    The covalent crosslinking of histones to DNA by UV laser irradiation is accomplished solely via the N-terminal part of the molecule. Irradiated isolated calfthymus nuclei are treated with clostripain. The crosslinked protein-DNA complexes are isolated and the presence of each core histone analyzed by dot-immunoassay using antibodies, specific to the central globular domain of the respective histone. The reaction is negative for all core histones i.e. the globular domain is absent. It means that this domain has not been crosslinked to DNA and, once cleaved by clostripain, it has been stripped from DNA during the centrigugation in CsCl. This peculiar property of the crosslinked procedure makes it particularly useful in addressing some yet unanswered questions concerning histone-DNA interactions, such as the interaction of the N-terminal tails with linker DNA, the effect of the transient postsynthetic histone acetylation on its interaction with DNA, etc. These questions are now under study. 1 fig., 6 refs

  2. Cystatin C, N-terminal probrain natriuretic peptides and outcomes in acute heart failure with acute kidney injury in a 12-month follow-up: Insights into the cardiorenal syndrome

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    Zhong-bao Ruan

    2014-01-01

    Full Text Available Background: Cystatin C (Cys C has been implicated as a prognostic marker in cardiovascular disease. The aim of this study was to evaluate the value of Cys C as a marker of acute kidney injury (AKI in acute heart failure (AHF, the impact of Cys C and N-terminal probrain natriuretic peptides (NT-proBNP on in-hospital and 12 months mortality were also investigated. Materials and Methods: A total of 162 patients with AHF were enrolled. NT-proBNP, Cys C, serum creatinine (Scr, blood urea nitrogen (BUN and parameters of echocardiography were measured for analyze. The in-hospital and 12 months mortality was analyzed. Results: There was 28 (17% of all AHF patients with AKI. Compared with no-AKI patients, the levels of Cys C (1.51 ± 0.34 vs. 1.32 ± 0.29, P = 0.003 and NT-proBNP (8163.87 ± 898.06 vs. 5922.45 ± 576.73, P = 0.001 were higher in AKI patients. Higher levels of NT-proBNP (odds ratio (OR = 1.92, 95% confidence interval (CI: 2.19-10.98, P = 0.018, OR = 4.31, 95% CI: 2.35-9.82, P = 0.002, respectively and Cys C (OR = 1.48, 95% CI: 1.75-4.16, P = 0.027, OR = 2.72, 95% CI: 1.92-4.28, P = 0.017, respectively were independent association with the in-hospital and 12 months mortality. Cys C was positively correlated with NT-proBNP (r = 0.87, P < 0.001. Combining tertiles of Cys C and NT-proBNP improved risk stratification further. Compared with patients without AKI cysC , patients with AKI cysC was associated with higher in-hospital (7/28 vs. 10/134, P = 0.002 and 12-month mortality (13/28 vs. 32/134, P = 0.001. Conclusion: Cys C was not only a promising risk marker in patients hospitalized for AHF, but also an independent predictor of 12-month mortality. Combining tertiles of Cys C and NT-proBNP could be used to distinguish the mortality risk identification of patients with AHF. AKI was an independent predictor of in-hospital and 12-month mortality.

  3. Serum levels of N-terminal-pro B-type natriuretic peptide as a diagnostic marker for left ventricular dysfunction in children with end-stage renal disease on hemodialysis

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    Amr Mohamed Zoair

    2016-01-01

    Full Text Available The objective of this study was to determine the diagnostic cutoff value of N-terminal-pro B-type natriuretic peptide (NT-pro BNP as a marker of left ventricular (LV dysfunction in children with end-stage renal disease (ESRD on regular hemodialysis (HD. The study was carried out on thirty children with ESRD on regular HD and thirty healthy controls. Echocardiographic studies were done, including a conventional mode for ejection fraction, fractional shortening, tissue Doppler imaging, and longitudinal global strain by speckle tracking. Serum levels of NT-pro BNP were measured in venous blood samples before and about 30 min after HD by ELISA. Volume status was assessed by calculating interdialytic weight gain %. There were significant higher serum NT-pro BNP levels before HD (mean: 702.3 ± 274.3 ng/L compared to controls (mean: 365.55 ± 76.5 ng/L (P <0.001 and these levels decreased significantly after the HD session (mean: 625.1 ± 117.69 ng/L (P = 0.031. Echocardiographic studies showed a significant impairment of LV function of the patients compared to controls. Patients with LV dysfunction had significant higher serum concentrations of NT-pro BNP compared to patients without dysfunction both before (P = 0.003 and after dialysis (P <0.001. Receiver operating curve demonstrated better prediction of LV dysfunction by NT-pro BNP levels after HD compared to its levels before HD (area under the curve was 0.9 and 0.73, respectively. Using a cutoff value of 630 ng/L, serum NT-pro BNP levels after dialysis were a diagnostic predictor of LV dysfunction with a sensitivity of 86.6%, specificity of 93.3%, positive predictive value of 92.8%, and negative predictive value of 87.5%. Serum NT-pro BNP levels were strongly correlated with the parameters of LV dysfunction in children with ESRD on regular HD. A postdialysis cutoff value of 630 ng/L could serve as a biochemical marker of LV dysfunction in those children regardless of chronic fluid overload.

  4. Plasma Levels of Monocyte Chemoattractant Protein-1, n-Terminal Fragment of Brain Natriuretic Peptide and Calcidiol Are Independently Associated with the Complexity of Coronary Artery Disease.

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    Roberto Martín-Reyes

    Full Text Available We investigated the relationship of the Syntax Score (SS and coronary artery calcification (CAC, with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field.We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0-1 and high-grade (2-3 calcification, measured with a semiquantitative scale ranging from 0 (none to 3 (severe. For the SS study patients were divided in SS<14 and SS≥14. Multivariate linear and logistic regression analyses were performed.MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08-3.39]; p = 0.040, along with NT-proBNP (RC = 0.17 [95%CI = 0.05-0.28]; p = 0.004, male sex (RC = 4.15 [95%CI = 1.47-6.83]; p = 0.003, age (RC = 0.13 [95%CI = 0.02-0.24]; p = 0.020, hypertension (RC = 3.64, [95%CI = 0.77-6.50]; p = 0.013, hyperlipidemia (RC = 2.78, [95%CI = 0.28-5.29]; p = 0.030, and statins (RC = 6.12 [95%CI = 1.28-10.96]; p = 0.013. Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36-0.90]; p = 0.013 along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19-0.78]; p = 0.006, diabetes (OR = 2.35 [95%CI = 1.11-4.98]; p = 0.028 and age (OR = 1.37 [95%CI = 1.18-1.59]; p<0.001. During follow-up (1.79 [0.94-2.86] years, 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome.MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels are associated with CAC. More studies are needed to confirm these data.

  5. The effectiveness of the treatment of severe exercise-induced asthma in schoolchildren

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    M.N. Garas

    2017-03-01

    Full Text Available Background. Bronchial asthma is one of the most common chronic multifactorial diseases of the lungs. At least 10–12 % of patients with bronchial asthma are suffering from a severe form of the disease. One aspect of inadequate severe asthma control is its phenotypic heterogeneity, interest of experts increases to the problem of exercise-induced asthma. The purpose of the study was to increase efficiency of treatment for severe exercise-induced asthma in schoolchildren based on the analysis of the attack dynamics and to achieve disease control according to main inflammatometric and spirometric indices. Materials and methods. We examined 46 children with severe persistent bronchial asthma, in particular, 15 schoolchildren suffering from severe exercise-induced asthma, the second clinical group (comparison one consisted of 31 children suffering from severe type of the disease, with no signs of exercise-induced bronchoconstriction. Basic therapy effectiveness was determined prospectively by assessing the disease control using AST-test with an interval of 3 months. The severity of bronchial obstruction syndrome in patients on admission to hospital during exacerbation was assessed by score scale. Airway hyperresponsiveness was evaluated according to the results of bronchoprovocation with histamine. Results. Children of I clinical group had more significant manifestations of bronchial obstruction during the week of inpatient treatment than the comparison group of patients, including significantly more severe manifestations of bronchial obstruction were verified on 1st and 7th day of hospitalization. Due to the analysis of basic therapy effectiveness, only a quarter of I clinical group patients and a larger part of schoolchildren in comparison group achieved the partial control after a 3-month course of anti-inflammatory treatment. Eosinophilic inflammation was observed in most children with severe exercise-induced asthma (60.1 % and in 47.2 % of

  6. A systematic review of BNP and NT-proBNP in the management of heart failure: overview and methods.

    Science.gov (United States)

    Oremus, Mark; McKelvie, Robert; Don-Wauchope, Andrew; Santaguida, Pasqualina L; Ali, Usman; Balion, Cynthia; Hill, Stephen; Booth, Ronald; Brown, Judy A; Bustamam, Amy; Sohel, Nazmul; Raina, Parminder

    2014-08-01

    B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels are increased in persons with heart failure (HF); low levels of these peptides rule out HF. We systematically reviewed the literature to assess the use of BNP and NT-proBNP in the diagnosis, prognosis, and treatment for HF. We also examined the biological variation of these peptides in persons with and without HF. We searched Medline, Embase, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL for English-language studies published between January 1989 and June 2012. Supplemental searches involved the gray literature and the reference lists of included studies. Trained reviewers used standardized forms to screen articles for inclusion in the review and to extract data from included papers. We examined the risk of bias with QUADAS-2 for diagnosis studies, the Hayden criteria for prognosis studies, and the Jadad scale for treatment studies. We assessed the strength of evidence in four domains (risk of bias, consistency, directness, and precision) for the diagnosis and treatment studies. Results were reported as narrative syntheses. Additional meta-analyses were conducted for the diagnosis studies. Three hundred ten articles passed through screening and were included in the review. One hundred four articles applied to diagnostic accuracy, 190 papers pertained to prognosis, and nine articles addressed BNP- or NT-proBNP-guided treatment. Each individual paper in this series reports, summarizes, and discusses the evidence regarding diagnosis, prognosis, or treatment.

  7. Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain.

    Science.gov (United States)

    Moparthi, Lavanya; Survery, Sabeen; Kreir, Mohamed; Simonsen, Charlotte; Kjellbom, Per; Högestätt, Edward D; Johanson, Urban; Zygmunt, Peter M

    2014-11-25

    We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1-688 hTRPA1) is intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that electrophilic compounds activate hTRPA1 in the presence and absence of the N-terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Δ(9)-tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites independent of the N-terminal ARD. The TRPA1 antagonist HC030031 inhibited cold and chemical activation of hTRPA1 and Δ1-688 hTRPA1, supporting a direct interaction with hTRPA1 outside the N-terminal ARD. These findings show that hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second messengers, including Ca(2+), or accessory proteins are not needed for hTRPA1 responses to cold or chemical activators. We suggest that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are important in hTRPA1 channel gating and that targeting chemical interaction sites outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug therapies (e.g., for treatment of pain associated with cold hypersensitivity and cardiovascular disease).

  8. Isotope-coded N-terminal sulfonation of peptides allows quantitative proteomic analysis with increased de novo peptide sequencing capability.

    Science.gov (United States)

    Lee, Yong Ho; Han, Hoon; Chang, Seok-Bok; Lee, Sang-Won

    2004-01-01

    Recently various methods for the N-terminal sulfonation of peptides have been developed for the mass spectrometric analyses of proteomic samples to facilitate de novo sequencing of the peptides produced. This paper describes the isotope-coded N-terminal sulfonation (ICenS) of peptides; this procedure allows both de novo peptide sequencing and quantitative proteomics to be studied simultaneously. As N-terminal sulfonation reagents, 13C-labeled 4-sulfophenyl[13C6]isothiocyanate (13C-SPITC) and unlabeled 4-sulfophenyl isothiocyanate (12C-SPITC) were synthesized. The experimental and reference peptide mixtures were derivatized independently using 13C-SPITC and 12C-SPITC and then combined to generate an isotopically labeled peptide mixture in which each isotopic pair differs in mass by 6 Da. Capillary reverse-phase liquid chromatography/tandem mass spectrometry experiments on the resulting peptide mixtures revealed several immediate advantages of ICenS in addition to the de novo sequencing capability of N-terminal sulfonation, namely, differentiation between N-terminal sulfonated peptides and unmodified peptides in mass spectra, differentiation between N- and C-terminal fragments in tandem mass spectra of multiply protonated peptides by comparing fragmentations of the isotopic pairs, and relative peptide quantification between proteome samples. We demonstrate that the combination of N-terminal sulfonation and isotope coding in the mass spectrometric analysis of proteomic samples is a viable method that overcomes many problems associated with current N-terminal sulfonation methods. Copyright 2004 John Wiley & Sons, Ltd.

  9. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients.

    Science.gov (United States)

    Slagman, Maartje C J; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D

    2012-03-01

    Renin-angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both under- and overtitration of sodium targeting can easily occur. We evaluated whether N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of volume expansion, predicts the benefits of sodium targeting in CKD patients. In a cross-over randomized controlled trial, 33 non-diabetic CKD patients (proteinuria 3.8 ± 0.4 g/24 h, blood pressure 143/86 ± 3/2 mmHg, creatinine clearance 89 ± 5 mL/min) were treated during 6-week periods with placebo, angiotensin receptor blockade (ARB; losartan 100 mg/day) and ARB plus diuretics (losartan 100 mg/day plus hydrochlorothiazide 25 mg/day), combined with LS (93 ± 52 mmol Na(+)/24 h) and regular sodium diet (RS; 193 ± 62 mmol Na(+)/24 h, P diuretics and was normalized by ARB + diuretic + LS [39 (26-59) pg/mL, P = 0.65 versus controls]. NT-proBNP levels above the upper limit of normal (>125 pg/mL) predicted a larger reduction of blood pressure and proteinuria by LS and diuretics but not by ARB, during all steps of the titration regimen. Elevated NT-proBNP levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of sodium targeting, but not RAAS blockade, in proteinuric CKD patients. Importantly, this applies to the untreated condition, as well as to the subsequent treatment steps, consisting of RAAS blockade and even RAAS blockade combined with diuretics. NT-proBNP can be a useful tool to identify CKD patients in whom sodium targeting can improve blood pressure and proteinuria.

  10. NT Security in an Open Academic Environment

    Energy Technology Data Exchange (ETDEWEB)

    Cowles, Robert D

    1999-06-02

    Stanford Linear Accelerator Center (SLAC) was faced with the need to secure its PeopleSoft-Oracle business system in an academic environment that has no firewall. To provide protected access to the database servers for NT-based users all over the site while not hindering the lab's open connectivity with the Internet, we implemented a pseudo three-tier architecture for PeopleSoft with Windows Terminal Server and Citrix MetaFrame technology. The client application and Oracle database were placed behind a firewall, and access was granted via an encrypted link to a thin client. Authentication in the future will be through two-factor token cards. NT workstations in the business system unit were further secured through switched network ports and an automated installation process that included SMB signing and disabling LM Authentication in favor of NTLMv2. The hardened workstations then accessed the business system through the Citrix Secure ICA client. How these security measures affected our mixed environment (Windows9x, Samba, Transarc AFS clients, Pathworks, developers, researchers) is discussed.

  11. N-terminal N-myristoylation of proteins: prediction of substrate proteins from amino acid sequence.

    Science.gov (United States)

    Maurer-Stroh, Sebastian; Eisenhaber, Birgit; Eisenhaber, Frank

    2002-04-05

    Myristoylation by the myristoyl-CoA:protein N-myristoyltransferase (NMT) is an important lipid anchor modification of eukaryotic and viral proteins. Automated prediction of N-terminal N-myristoylation from the substrate protein sequence alone is necessary for large-scale sequence annotation projects but it requires a low rate of false positive hits in addition to a sufficient sensitivity. Our previous analysis of substrate protein sequence variability, NMT sequences and 3D structures has revealed motif properties in addition to the known PROSITE motif that are utilized in a new predictor described here. The composite prediction function (with separate ad hoc parameterization (a) for queries from non-fungal eukaryotes and their viruses and (b) for sequences from fungal species) consists of terms evaluating amino acid type preferences at sequences positions close to the N terminus as well as terms penalizing deviations from the physical property pattern of amino acid side-chains encoded in multi-residue correlation within the motif sequence. The algorithm has been validated with a self-consistency and two jack-knife tests for the learning set as well as with kinetic data for model substrates. The sensitivity in recognizing documented NMT substrates is above 95 % for both taxon-specific versions. The corresponding rate of false positive prediction (for sequences with an N-terminal glycine residue) is close to 0.5 %; thus, the technique is applicable for large-scale automated sequence database annotation. The predictor is available as public WWW-server with the URL http://mendel.imp.univie.ac.at/myristate/. Additionally, we propose a version of the predictor that identifies a number of proteolytic protein processing sites at internal glycine residues and that evaluates possible N-terminal myristoylation of the protein fragments.A scan of public protein databases revealed new potential NMT targets for which the myristoyl modification may be of critical importance for

  12. Impact-driven, pulmonary emboli of osseous fat in exercise-induced bronchospasm.

    Science.gov (United States)

    Simkin, Peter A; Snitily, Brian K

    2015-11-01

    Exercise induced bronchospasm (EIB) affects approximately 10% of normal individuals with higher prevalence rates among children, obese adults, and competitive athletes. Although hyperpnea with dry air is the best known cause, the problem is multifactorial with atopy, asthma and chlorine all playing established roles. To date, no clear mechanism has connected musculoskeletal loading with the ensuing pulmonary compromise. This paper reviews evidence that impact-driven pulses in subchondral bone pressure may push osseous fat cells into the local venous sinusoids. The resultant showers of microemboli must then travel to the lung where lysis of membrane phospholipids leads to leukotriene formation with resultant inflammation and bronchial hypersensitivity. Concurrently, the same emboli deliver triglyceride fuels for further physical activity. Thus, pulmonary microemboli derived from osseous fat may resolve the seeming paradox of athletic excellence in persons afflicted with exercise-induced bronchospasm. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Exercise-Induced Cardiac Remodeling: Lessons from Humans, Horses, and Dogs.

    Science.gov (United States)

    Shave, Rob; Howatson, Glyn; Dickson, Dave; Young, Lesley

    2017-02-12

    Physical activity is dependent upon the cardiovascular system adequately delivering blood to meet the metabolic and thermoregulatory demands of exercise. Animals who regularly exercise therefore require a well-adapted heart to support this delivery. The purpose of this review is to examine cardiac structure, and the potential for exercise-induced cardiac remodeling, in animals that regularly engage in strenuous activity. Specifically, we draw upon the literature that has studied the "athlete's heart" in humans, horses, and dogs, to enable the reader to compare and contrast cardiac remodeling in these three athletic species. The available literature provides compelling evidence for exercise-induced cardiac remodeling in all three species. However, more work is required to understand the influence of species/breed specific genetics and exercise-related hemodynamics, in order to fully understand the impact of exercise on cardiac structure.

  14. Exercise-induced rib stress fractures: influence of reduced bone mineral density

    DEFF Research Database (Denmark)

    Vinther, Anders; Kanstrup, Inge-Lis; Christiansen, Erik

    2005-01-01

    Exercise-induced rib stress fractures have been reported frequently in elite rowers during the past decade. The etiology of rib stress fractures is unclear, but low bone mineral density (BMD) has been suggested to be a potential risk factor for stress fractures in weight-bearing bones. The present...... study investigated BMD in seven Danish national team rowers with previous rib stress fracture (RSF) and 7 controls (C) matched for gender, age, height, weight and training experience. Total body scan and specific scans of the lumbar spine (L2-L4), femoral neck and distal radius were performed using...... density may be a potential risk factor for the development of exercise-induced rib stress fractures in elite rowers....

  15. Polyphenols in Exercise Performance and Prevention of Exercise-Induced Muscle Damage

    Directory of Open Access Journals (Sweden)

    Marco Malaguti

    2013-01-01

    Full Text Available Although moderate physical exercise is considered an essential component of a healthy lifestyle that leads the organism to adapt itself to different stresses, exercise, especially when exhaustive, is also known to induce oxidative stress, inflammation, and muscle damage. Many efforts have been carried out to identify dietary strategies or micronutrients able to prevent or at least attenuate the exercise-induced muscle damage and stress. Unfortunately most studies have failed to show protection, and at the present time data supporting the protective effect of micronutrients, as antioxidant vitamins, are weak and trivial. This review focuses on those polyphenols, present in the plant kingdom, that have been recently suggested to exert some positive effects on exercise-induced muscle damage and oxidative stress. In the last decade flavonoids as quercetin, catechins, and other polyphenols as resveratrol have caught the scientists attention. However, at the present time drawing a clear and definitive conclusion seems to be untimely.

  16. On the value of certain genotypic properties for forming exercise-induced bronchial asthma in children

    Directory of Open Access Journals (Sweden)

    Лорина Алімівна Іванова

    2015-10-01

    Full Text Available Introduction. Exercise-induced bronchial asthma is a separate phenotype of bronchial asthma (BA that defines an exercise-associated transitory obstruction of bronchial tubes, especially decrease of the forced expiration volume for 1 sec. (FEV1 by 10 % and more of an output quantity after the relevant bronchial provocation test. At the same time there is not sufficient elucidation of the role of genetic component especially GSTT1 і GSTM1 gene deletions and\\or mutational polymorphism of еNOS gene in development of exercise-induced bronchial asthma in children.Aim. To study the value of deletion (GSTT1 and GSTM1 genes and mutational (еNOS gene polymorphism in formation of bronchial tubes lability in children with exercise-induced bronchial asthma to optimize individual medioprophylactic recommendations.Materials and methods. During the study there were examined 102 school-aged children with BA in pulmo-allergology department of RSCH in Chernovtsy. To verify the exercise-induced bronchial asthma (EIBA there was studied an exercise tolerance of patients and their bronchial tubes lability in the response to the dosed run and bronchomotor test with inhalation with 200 mkg of salbutamol. And the received results were represented as a bronchial tubes lability indicator (BTLI, % and its components – bronchospasm index (BSI, % and bronchodilation index (BDI, %. 2 clinical groups were formed in examination of children. The first (I, main included 50 schoolchildren with EIBA and the comparative one (II group – 52 children with BA without the signs of exercise-induced bronchospasm (EIBS. Results of research. There was established that the “null” genotype of aforesaid genes is three times more often (10,0 % against 3,85 %, P<0,05in children with exercise-induced bronchial asthma and mutations of еNOS gene ( GT, ТТ genotype take place in every second children. There was detected that the highest bronchospasm indicators are in patients with GSTT1

  17. Exercise-Induced Cardiac Remodeling: Lessons from Humans, Horses, and Dogs

    Directory of Open Access Journals (Sweden)

    Rob Shave

    2017-02-01

    Full Text Available Physical activity is dependent upon the cardiovascular system adequately delivering blood to meet the metabolic and thermoregulatory demands of exercise. Animals who regularly exercise therefore require a well-adapted heart to support this delivery. The purpose of this review is to examine cardiac structure, and the potential for exercise-induced cardiac remodeling, in animals that regularly engage in strenuous activity. Specifically, we draw upon the literature that has studied the “athlete’s heart” in humans, horses, and dogs, to enable the reader to compare and contrast cardiac remodeling in these three athletic species. The available literature provides compelling evidence for exercise-induced cardiac remodeling in all three species. However, more work is required to understand the influence of species/breed specific genetics and exercise-related hemodynamics, in order to fully understand the impact of exercise on cardiac structure.

  18. N-terminal Pro-Brain Natriuretic Peptide And Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Jayachandran Thejus

    2009-01-01

    Full Text Available NT-proBNP is produced from both atria and ventricles. The primary regulation of production is at the synthesis level. The plasma half-life of NT-proBNP is 60-120 min. Cutoff value of NT-proBNP for diagnosis of heart failure is 125 pg/ml in the age group below 75 years and 450 pg/ml in the age group above 75 years. It increases in atrial fibrillation and drops after successful cardioversion. High levels predict development of atrial fibrillation (AF in healthy persons with sinus rhythm (SR. Some studies concluded that baseline level predicts maintenance of SR after cardioversion of AF while some others found that it did not. Many studies have proven that it is useful in monitoring rhythm stability after cardioversion of AF. Since it is increased in many other conditions, out of which some may also cause AF, care must be taken before ascribing changes in its level to AF alone.

  19. Strength and Fatigue of NT551 Silicon Nitride and NT551 Diesel Exhaust Valves

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, M.J.; Wereszczak, A.A.; Kirkland, T.P.; Breder, K.

    2000-02-01

    The content of this report is excerpted from Mark Andrew's Ph.D. Thesis (Andrews, 1999), which was funded by a DOEYOTT High Temperature Materials Laboratory Graduate Fellowship. It involves the characterization of NT551 and valves fabricated with it. Greater detail of the described issues may be found in that reference or through communications with Andrew Wereszczak.

  20. Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Philip P. Foster

    2011-05-01

    Full Text Available Lifestyle factors such as intellectual stimulation, cognitive and social engagement, nutrition, and various types of exercise appear to reduce the risk for common age-associated disorders such as Alzheimer’s disease (AD and vascular dementia. In fact, many studies have suggested that promoting physical activity can have a protective effect against cognitive deterioration later in life. Slowing or a deterioration of walking speed is associated with a poor performance in tests assessing psychomotor speed and verbal fluency in elderly individuals. Fitness training influences a wide range of cognitive processes, and the largest positive impact observed is for executive (a.k.a. frontal lobe functions. Studies show that exercise improves additional cognitive functions such as tasks mediated by the hippocampus, and result in major changes in plasticity in the hippocampus. Interestingly, this exercise-induced plasticity is also pronounced in APOE ε4 carriers who express a risk factor for late-onset AD that may modulate the effect of treatments. Based on AD staging by Braak et al., we propose that the effects of exercise occur in two temporo-spatial continua of events. The inward continuum from isocortex (neocortex to entorhinal cortex/hippocampus for amyloidosis and a reciprocal outward continuum for neurofibrillary alterations. The exercise-induced hypertrophy of the hippocampus at the core of these continua is evaluated in terms of potential for prevention to stave off neuronal degeneration. Exercise-induced production of growth factors such as the brain-derived neurotrophic factor (BDNF has been shown to enhance neurogenesis and to play a key role in positive cognitive effects. Insulin-like growth factor (IGF-1 may mediate the exercise-induced response to exercise on BDNF, neurogenesis and cognitive performance. It is also postulated to regulate brain amyloid β (Aβ levels by increased clearance via the choroid plexus. Growth factors

  1. High-fat feeding inhibits exercise-induced increase in mitochondrial respiratory flux in skeletal muscle

    DEFF Research Database (Denmark)

    Skovbro, Mette; Boushel, Robert Christopher; Hansen, Christina Neigaard

    2011-01-01

    -62%) were seen in HFD and ND, but only in HFD was an elevated (P respiratory rate seen at recovery. With HFD complex I and IV protein expression decreased (P system protein content......) and intramyocellular triacylglycerol content did not change with the intervention in either group. Indexes of mitochondrial density were similar across the groups and intervention. Mitochondrial respiratory rates, measured in permeabilized muscle fibers, showed a 31 ± 11 and 26 ± 9% exercise-induced increase (P

  2. Approach to the diagnosis and management of suspected exercise-induced bronchoconstriction by primary care physicians

    OpenAIRE

    Hull, James H; Hull, Peter J; Parsons, Jonathan P; Dickinson, John W; Ansley, Les

    2009-01-01

    Abstract Background Exercise-related respiratory symptoms in the diagnosis of exercise-induced bronchoconstriction (EIB) have poor predictive value. The aim of this study was to evaluate how athletes presenting with these symptoms are diagnosed and managed in primary care. Methods An electronic survey was distributed to a random selection of family practitioners in England. The survey was designed to assess the frequency with which family practitioners encounter adults with exercise-related r...

  3. Pretreatment with albuterol versus montelukast for exercise-induced bronchospasm in children.

    Science.gov (United States)

    Raissy, Hengameh H; Harkins, Michelle; Kelly, Franceska; Kelly, H William

    2008-03-01

    To compare pretreatment with albuterol versus montelukast added to the current asthma regimen for protection against exercise-induced bronchospasm in children with mild-to-moderate asthma, and to determine whether cysteinyl leukotriene (Cys-LT) concentrations measured in the exhaled breath condensate correlated with response to montelukast. Prospective, randomized, double-blind, double-dummy, crossover study. Asthma clinic at a university-affiliated medical center. Eleven children aged 7-17 years with physician-diagnosed mild-to-moderate asthma for at least 6 months and with self-reported exercise-induced bronchospasm (defined as > or = 15% decrease in forced expiratory volume in 1 sec [FEV(1)] at screening and baseline visit). Patients were randomly assigned to receive 3-7 days of oral montelukast 5-10 mg/day or 2 puffs of an albuterol metered-dose inhaler just before an exercise challenge and then were crossed over to the alternate therapy for the last visit. Serial spirometry was performed before and at 0, 5, 10, 15, 30, 45, and 60 minutes after the exercise challenge at each visit. Measurement of exhaled breath condensate was performed at the screening visit and study visits 1 and 2. The primary outcome was the maximum change in FEV(1) after exercise. Secondary outcomes were the area under the curve for FEV(1) (expressed as percentage decrease from baseline) during the first 60 minutes (AUC(0-60)) after exercise and the proportion of patients in whom exercise-induced bronchospasm was prevented (defined as bronchospasm was prevented in 100% of the patients receiving albuterol compared with 55% receiving montelukast (pbronchospasm or the response to montelukast. Pretreatment with albuterol is more effective than montelukast for prevention of exercise-induced bronchospasm in children with asthma.

  4. Bronchial provocation testing does not detect exercise-induced laryngeal obstruction

    DEFF Research Database (Denmark)

    Walsted, Emil Schwarz; Hull, James H; Sverrild, Asger

    2017-01-01

    INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) is a key differential diagnosis for asthma in the presence of exertional respiratory symptoms. Continuous laryngoscopy during exercise (CLE), the current gold standard diagnostic test for EILO, has practical limitations. We aimed...... to establish if inspiratory flow data obtained during standard bronchoprovocation testing, to establish the presence of extra-thoracic hyper-responsiveness, may prove diagnostic for EILO and thus preclude requirement for CLE testing. METHODS: We consecutively evaluated 37 adult subjects with exertional dyspnea...

  5. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    International Nuclear Information System (INIS)

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A.

    1990-01-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01)

  6. Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina

    International Nuclear Information System (INIS)

    Kugiyama, K.; Yasue, H.; Okumura, K.

    1988-01-01

    The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm

  7. Exercise-induced ischemic preconditioning detected by sequential exercise stress tests: a meta-analysis.

    Science.gov (United States)

    Lalonde, François; Poirier, Paul; Sylvestre, Marie-Pierre; Arvisais, Denis; Curnier, Daniel

    2015-01-01

    Exercise-induced ischemic preconditioning (IPC) can be assessed with the second exercise stress test during sequential testing. Exercise-induced IPC is defined as the time to 1 mm ST segment depression (STD), the rate-pressure product (RPP) at 1 mm STD, the maximal ST depression and the rate-pressure product at peak exercise. The purpose of this meta-analysis is to validate the parameters used to assess exercise-induced IPC in the scientific community. A literature search was performed using electronic database. The main key words were limited to human studies, which were (a) ischemic preconditioning, (b) warm-up phenomenon, and (c) exercise. Meta-analyses were performed on the study-specific mean difference between the clinical measures obtained in the two consecutive stress tests (second minus first test score). Random effect models were fitted with inverse variance weighting to provide greater weight to studies with larger sample size and more precise estimates. The search resulted in 309 articles of which 34 were included after revision (1053 patients). Results are: (a) time to 1 mm ST segment depression increased by 91 s (95% confidence interval (CI): 75-108), p ischemic preconditioning in sequential stress testing. The results of this first meta-analysis on the sequential stress test confirm what is presented in the literature by independent studies on exercise-induced ischemic preconditioning. From now on, the results could be used in further research to set standardized parameters to assess the phenomenon. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. Exercise-induced bronchoconstriction and non-specific airway hyperreactivity in patients suffering from bronchial asthma.

    Science.gov (United States)

    Novković, Dobrivoje; Skuletić, Vesna; Vulin, Aleksandra; Cvetković, Gordana

    2014-02-01

    Physical activity is a common stimulus of asthmatic symptoms manifestation. Airway hyperreactivity is a predisposing cause of exercise induced bronchial obstruction, diagnosed by histamine inhalation. The aim of this study was to determine the relation between the amounts of histamine needed to induce non-specific airway hyperreactivity and exercise-induced bronchial obstruction. This randomized cross-over study included 160 male patients (age 19-27 years) suffering from bronchial asthma who showed positive results as the reaction after the histamine bronchial provocation test. Histamine concentrations were in a range of 0.03 to 4 mg/mL. Each patient participated in the exercise stress test conducted on a conveyor belt. The results of the exercise stress test were considered positive if the FEV1 level dropped by at least 15% from its initial value, 5-10 minutes after the test. All the patients showed positive results as the reaction after the histamine bronchial provocation test, while 50 of them showed positive results after the exercise-induced stress test. There was a statistically highly significant difference in administrated histamine concentrations between the group of patients that had positive results on exercise stress test and those who did not (1 mg/mL vs 0.5 mg/mL; U = 1678; p exercise stress test (p exercise-induced stress test, there were significantly more patients with positive results to non-specific bronchial provocation test with lower histamine concentrations. Histamine concentrations needed to induce non-specific hyperreactivity of asthmatic airway were shown to be related to the reactivity to physical effort.

  9. Allergies and Exercise-Induced Bronchoconstriction in a Youth Academy and Reserve Professional Soccer Team.

    Science.gov (United States)

    Bougault, Valérie; Drouard, François; Legall, Franck; Dupont, Grégory; Wallaert, Benoit

    2017-09-01

    A high prevalence of respiratory allergies and exercise-induced bronchoconstriction (EIB) has been reported among endurance athletes. This study was designed to analyze the frequency of sensitization to respiratory allergens and EIB in young soccer players. Prospective cohort design. Youth academy and reserve professional soccer team during the seasons 2012 to 2013 and 2013 to 2014. Eighty-five soccer players (mean age: 20 ± 4 years) participated. Players underwent skin prick tests (SPTs) during the seasons 2012 to 2013 and 2013 to 2014. Spirometry and a eucapnic voluntary hyperpnea test were performed on soccer players during the first season 2012 to 2013 (n = 51) to detect EIB. Two self-administered questionnaires on respiratory history and allergic symptoms (European Community Respiratory Health Survey and Allergy Questionnaire for Athletes) were also distributed during both seasons (n = 59). The number of positive SPTs, exercise-induced respiratory symptoms, presence of asthma, airway obstruction, and EIB. Forty-nine percent of players were sensitized to at least one respiratory allergen, 33% reported an allergic disease, 1 player presented airway obstruction at rest, and 16% presented EIB. Factors predictive of EIB were self-reported exercise-induced symptoms and sensitization to at least 5 allergens. Questioning players about exercise-induced respiratory symptoms and allergies as well as spirometry at the time of the inclusion medical checkup would improve management of respiratory health of soccer players and would constitute inexpensive preliminary screening to select players requiring indirect bronchial provocation test or SPTs. This study showed that despite low frequencies, EIB and allergies are underdiagnosed and undertreated in young soccer players.

  10. Exercise excess pressure and exercise-induced albuminuria in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Climie, Rachel E D; Srikanth, Velandai; Keith, Laura J; Davies, Justin E; Sharman, James E

    2015-05-01

    Exercise-induced albuminuria is common in patients with type 2 diabetes mellitus (T2DM) in response to maximal exercise, but the response to light-moderate exercise is unclear. Patients with T2DM have abnormal central hemodynamics and greater propensity for exercise hypertension. This study sought to determine the relationship between light-moderate exercise central hemodynamics (including aortic reservoir and excess pressure) and exercise-induced albuminuria. Thirty-nine T2DM (62 ± 9 yr; 49% male) and 39 nondiabetic controls (53 ± 9 yr; 51% male) were examined at rest and during 20 min of light-moderate cycle exercise (30 W; 50 revolutions/min). Albuminuria was assessed by the albumin-creatinine ratio (ACR) at rest and 30 min postexercise. Hemodynamics recorded included brachial and central blood pressure (BP), aortic stiffness, augmented pressure (AP), aortic reservoir pressure, and excess pressure integral (Pexcess). There was no difference in ACR between groups before exercise (P > 0.05). Exercise induced a significant rise in ACR in T2DM but not controls (1.73 ± 1.43 vs. 0.53 ± 1.0 mg/mol, P = 0.002). All central hemodynamic variables were significantly higher during exercise in T2DM (i.e., Pexcess, systolic BP and AP; P exercise Pexcess was associated with postexercise ACR (r = 0.51, P = 0.002), and this relationship was independent of age, sex, body mass index, heart rate, aortic stiffness, antihypertensive medication, and ambulatory daytime systolic BP (β = 0.003, P = 0.003). Light-moderate exercise induced a significant rise in ACR in T2DM, and this was independently associated with Pexcess, a potential marker of vascular dysfunction. These novel findings suggest that Pexcess could be important for appropriate renal function in T2DM. Copyright © 2015 the American Physiological Society.

  11. Paradoxical vocal fold motion in children presenting with exercise induced dyspnea.

    Science.gov (United States)

    Hseu, Anne; Sandler, Mykayla; Ericson, Dawn; Ayele, Nohamin; Kawai, Kosuke; Nuss, Roger

    2016-11-01

    Although dyspnea with exercise in the pediatric population can be multifactorial, the diagnosis of paradoxical vocal fold motion disorder (PVFMD) in this group is not well characterized. The objective of this study is to review the multiple causes of dyspnea with exercise in children, including the prevalence of PVFMD within this study population. A retrospective review was conducted of patients seen at a tertiary pediatric hospital for exercise-induced dyspnea suspected to be related to PVFMD between January 2007 and July 2015. Inclusion criteria included assessment in a specialty exercise clinic and evaluation by a pediatric otolaryngologist and pulmonologist. Pre- and post-exercise pulmonary function tests and laryngoscopic examinations were performed. Data including co-morbidities, presenting symptoms, prior diagnoses and treatments, final diagnoses, prescribed treatments and outcomes were collected and analyzed. 294 patients were evaluated at our institution during the study period. 4 patients were excluded for insufficient data, which left 290 for analysis. 75 were male, 215 female. All patients underwent treadmill testing with monitoring to simulate strenuous exercise. Average patient age was 14.6 years; average BMI was 21.53. The most common sports to elicit symptoms were running and soccer. Patients most frequently complained of stridor or wheezing in addition to dyspnea. Throat tightness was also a common complaint. After evaluation, 86 patients were given the primary diagnosis of exercise-induced PVFMD. 54 patients were diagnosed with physiologic dyspnea and 30 with exercise-induced asthma. Pediatric patients presenting with exercise-induced dyspnea can have multiple etiologies for their symptoms including PVFMD. Other causes of dyspnea with exercise should not be underestimated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Annexin A2 is SUMOylated on its N-terminal domain: regulation by insulin.

    Science.gov (United States)

    Caron, Danielle; Boutchueng-Djidjou, Martial; Tanguay, Robert M; Faure, Robert L

    2015-04-13

    Insulin receptor (IR) endocytosis requires a remodelling of the actin cytoskeleton. We show here that ANXA2 is SUMOylated at the K10 located in a non-consensus SUMOylation motif in the N-terminal domain. The Y24F mutation decreased the SUMOylation signal, whereas insulin stimulation increased ANXA2 SUMOylation. A survey of protein SUMOylation in hepatic Golgi/endosome (G/E) fractions after insulin injections revealed the presence of a SUMOylation pattern and confirmed the SUMOylation of ANXA2. The construction of an IR/ANXA2/SUMO network (IRASGEN) in the G/E context reveals the presence of interacting nodes whereby SUMO1 connects ANXA2 to actin and microtubule-mediated changes in membrane topology. Heritable variants associated with type 2 diabetes represent 41% of the IRASGEN thus pointing out the physio-pathological importance of this subnetwork. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. Structure of the N-terminal fragment of topoisomerase V reveals a new family of topoisomerases

    Energy Technology Data Exchange (ETDEWEB)

    Taneja, Bhupesh; Patel, Asmita; Slesarev, Alexei; Mondragon, Alfonso (NWU); (FSI)

    2010-09-02

    Topoisomerases are involved in controlling and maintaining the topology of DNA and are present in all kingdoms of life. Unlike all other types of topoisomerases, similar type IB enzymes have only been identified in bacteria and eukarya. The only putative type IB topoisomerase in archaea is represented by Methanopyrus kandleri topoisomerase V. Despite several common functional characteristics, topoisomerase V shows no sequence similarity to other members of the same type. The structure of the 61 kDa N-terminal fragment of topoisomerase V reveals no structural similarity to other topoisomerases. Furthermore, the structure of the active site region is different, suggesting no conservation in the cleavage and religation mechanism. Additionally, the active site is buried, indicating the need of a conformational change for activity. The presence of a topoisomerase in archaea with a unique structure suggests the evolution of a separate mechanism to alter DNA.

  14. Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding.

    Science.gov (United States)

    Sandikci, Arzu; Gloge, Felix; Martinez, Michael; Mayer, Matthias P; Wade, Rebecca; Bukau, Bernd; Kramer, Günter

    2013-07-01

    Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates with ribosomes through a charged loop that is crucial for nascent-chain processing and cell viability. MAP competes with peptide deformylase (PDF), the first enzyme to act on nascent chains, for binding sites at the ribosomal tunnel exit. PDF has extremely fast association and dissociation kinetics, which allows it to frequently sample ribosomes and ensure the processing of nascent chains after their emergence. Premature recruitment of the chaperone trigger factor, or polypeptide folding, negatively affect processing efficiency. Thus, the fast ribosome association kinetics of PDF and MAP are crucial for the temporal separation of nascent-chain processing from later maturation events, including chaperone recruitment and folding.

  15. The Use of N-Terminal-Pro-BNP in Preterm Infants

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    Afif EL-Khuffash

    2009-01-01

    Full Text Available The use of natriuretic peptides in the neonatal population is emerging. B-type Natriuretic Peptide (BNP and N-terminal-Pro-BNP (NTpBNP are used in the adult population to assess myocardial function and volume loading. Their role in prognosis following cardiac surgery has also been identified. In preterm infants NTpBNP is becoming increasingly recognised as a potential screening tool for patent ductus arteriosus (PDA, and a marker for myocardial performance. In addition, NTpBNP may provide prognostic information in preterm infants and term infants with congenital diaphragmatic hernia (CDH. In this paper, the role of NTpBNP in the preterm population will be discussed.

  16. N-terminal region of human ameloblastin synthetic peptide promotes bone formation.

    Science.gov (United States)

    Kitagawa, Masae; Ando, Toshinori; Subarnbhesaj, Ajiravudh; Uchida, Takashi; Miyauchi, Mutsumi; Takata, Takashi

    2017-01-01

    The aim of this study was to examine the effect of 16 amino acids of the N-terminal region of human ameloblastin (16N-AMBN) synthetic peptide, on the proliferation and differentiation of MC3T3-E1 cells and bone regeneration. While 16N-AMBN did not affect the proliferation, it induced mRNA expression of type I collagen, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin. 16N-AMBN also stimulated ALP activity and promoted mineralized nodule formation. On the other hand, these activities were inhibited by anti-16N-AMBN antibody. Treatment of rat calvarial bone defects with 16N-AMBN resulted in almost complete healing compared to that of the control treatments. These findings suggest that 16N-AMBN may be applicable for regeneration therapy of bone defects.

  17. The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin

    DEFF Research Database (Denmark)

    Hasbak, Philip; Eskesen, Karen; Lind, Peter Henrik

    2006-01-01

    ) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection......In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenous neuropeptides calcitonin gene-related peptide (CGRP...... of the peptides. The mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction (real-time PCR). CGRP, adrenomedullin and amylin induced concentration-dependent, long-lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar...

  18. Crystallization of Galectin-8 Linker Reveals Intricate Relationship between the N-terminal Tail and the Linker

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    Yunlong Si

    2016-12-01

    Full Text Available Galectin-8 (Gal-8 plays a significant role in normal immunological function as well as in cancer. This lectin contains two carbohydrate recognition domains (CRD connected by a peptide linker. The N-terminal CRD determines ligand binding specificity, whereas the linker has been proposed to regulate overall Gal-8 function, including multimerization and biological activity. Here, we crystallized the Gal-8 N-terminal CRD with the peptide linker using a crystallization condition that contains Ni2+. The Ni2+ ion was found to be complexed between two CRDs via crystal packing contacts. The coordination between Ni2+ and Asp25 plays an indirect role in determining the structure of β-strand F0 and in influencing the linker conformation which could not be defined due to its dynamic nature. The linker was also shortened in situ and crystallized under a different condition, leading to a higher resolution structure refined to 1.08 Å. This crystal structure allowed definition of a short portion of the linker interacting with the Gal-8 N-terminal tail via ionic interactions and hydrogen bonds. Observation of two Gal-8 N-terminal CRD structures implies that the N-terminal tail and the linker may influence each other’s conformation. In addition, under specific crystallization conditions, glycerol could replace lactose and was observed at the carbohydrate binding site. However, glycerol did not show inhibition activity in hemagglutination assay.

  19. X-ray diffraction studies on merohedrally twinned Δ1-62NtNBCe1-A crystals of the sodium/bicarbonate cotransporter.

    Science.gov (United States)

    Gill, Harindarpal S; Dutcher, Lauren; Boron, Walter F; Patel, Samir; Guay-Woodford, Lisa M

    2013-07-01

    NBCe1-A membrane-embedded macromolecules that cotransport sodium and bicarbonate ions across the bilayer serve to maintain acid-base homeostasis throughout the body. Defects result in a number of renal and eye disorders, including type-II renal tubular acidosis and cataracts. Here, crystals of a human truncated mutant of the cytoplasmic N-terminal domain of NBCe1 (Δ1-62NtNBCe1-A) are reported that diffract X-rays to 2.4 Å resolution. The crystal symmetry of Δ1-62NtNBCe1-A is of space group P31 with pseudo-P3121 symmetry and it has a hemihedral twin fraction of 33.0%. The crystals may provide insight into the pathogenic processes observed in a subset of patients with truncating and point mutations in the gene encoding NBCe1.

  20. PERSONALITY DOES NOT INFLUENCE EXERCISE-INDUCED MOOD ENHANCEMENT AMONG FEMALE EXERCISERS

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    Andrew M. Lane

    2005-09-01

    Full Text Available The present study investigated the influence of personality on exercise-induced mood changes. It was hypothesised that (a exercise would be associated with significant mood enhancement across all personality types, (b extroversion would be associated with positive mood and neuroticism with negative mood both pre- and post-exercise, and (c personality measures would interact with exercise-induced mood changes. Participants were 90 female exercisers (M = 25.8 yr, SD = 9.0 yr who completed the Eysenck Personality Inventory (EPI once and the Brunel Mood Scale (BRUMS before and after a 60-minute exercise session. Median splits were used to group participants into four personality types: stable introverts (n = 25, stable extroverts (n = 20, neurotic introverts (n = 26, and neurotic extroverts (n = 19. Repeated measures MANOVA showed significant mood enhancement following exercise across all personality types. Neuroticism was associated with negative mood scores pre- and post-exercise but the effect of extroversion on reported mood was relatively weak. There was no significant interaction effect between exercise-induced mood enhancement and personality. In conclusion, findings lend support to the notion that exercise is associated with improved mood. However, findings show that personality did not influence this effect, although neuroticism was associated with negative mood

  1. Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function.

    Science.gov (United States)

    Stelzer, I; Kröpfl, J M; Fuchs, R; Pekovits, K; Mangge, H; Raggam, R B; Gruber, H-J; Prüller, F; Hofmann, P; Truschnig-Wilders, M; Obermayer-Pietsch, B; Haushofer, A C; Kessler, H H; Mächler, P

    2015-10-01

    Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Effects of a Strength Training Session After an Exercise Inducing Muscle Damage on Recovery Kinetics.

    Science.gov (United States)

    Abaïdia, Abd-Elbasset; Delecroix, Barthélémy; Leduc, Cédric; Lamblin, Julien; McCall, Alan; Baquet, Georges; Dupont, Grégory

    2017-01-01

    Abaïdia, A-E, Delecroix, B, Leduc, C, Lamblin, J, McCall, A, Baquet, G, and Dupont, G. Effects of a strength training session after an exercise inducing muscle damage on recovery kinetics. J Strength Cond Res 31(1): 115-125, 2017-The purpose of this study was to investigate the effects of an upper-limb strength training session the day after an exercise inducing muscle damage on recovery of performance. In a randomized crossover design, subjects performed the day after the exercise, on 2 separate occasions (passive vs. active recovery conditions) a single-leg exercise (dominant in one condition and nondominant in the other condition) consisting of 5 sets of 15 eccentric contractions of the knee flexors. Active recovery consisted of performing an upper-body strength training session the day after the exercise. Creatine kinase, hamstring strength, and muscle soreness were assessed immediately and 20, 24, and 48 hours after exercise-induced muscle damage. The upper-body strength session, after muscle-damaging exercise accelerated the recovery of slow concentric force (effect size = 0.65; 90% confidence interval = -0.06 to 1.32), but did not affect the recovery kinetics for the other outcomes. The addition of an upper-body strength training session the day after muscle-damaging activity does not negatively affect the recovery kinetics. Upper-body strength training may be programmed the day after a competition.

  3. A Comparison of Exercise-Induced Muscle Damage Following Maximal Eccentric Contractions in Men and Boys.

    Science.gov (United States)

    Deli, Chariklia K; Fatouros, Ioannis G; Paschalis, Vassilis; Georgakouli, Kalliopi; Zalavras, Athanasios; Avloniti, Alexandra; Koutedakis, Yiannis; Jamurtas, Athanasios Z

    2017-08-01

    Research regarding exercise-induced muscle-damage mainly focuses on adults. The present study examined exercise-induced muscle-damage responses in adults compared with children. Eleven healthy boys (10-12 y) and 15 healthy men (18-45 y) performed 5 sets of 15 maximal eccentric contractions of the knee extensors. Range of motion (ROM), delayed onset muscle soreness (DOMS) during squat and walking, and peak isometric, concentric and eccentric torque were assessed before, post, 24, 48, 72, and 96 hr postexercise. Creatine kinase (CK) activity was assessed before and 72 hr postexercise. Eccentric exercise resulted in DOMS during squat that persisted for up to 96h in men, and 48 hr in boys (p < .05), and DOMS during walking that persisted for up to 72 hr in men, and 48 hr in boys (p < .01). The ROM was lower in both age groups 48 hr postexercise (p < .001). Isometric (p < .001), concentric (p < .01) and eccentric (p < .01) force decreased post, and up to 48 hr postexercise in men. Except for a reduction in isometric force immediately after exercise, no other changes occurred in boys' isokinetic force. CK activity increased in men at 72 hr postexercise compared with pre exercise levels (p = .05). Our data provide further confirmation that children are less susceptible to exercise-induced muscle damage compared with adults.

  4. Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

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    Alexandra Sakelliou

    2016-01-01

    Full Text Available We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day immediately after a muscle-damaging exercise protocol (300 eccentric contractions and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation.

  5. Exercise-induced asthma: critical analysis of the protective role of montelukast

    Directory of Open Access Journals (Sweden)

    Terrence W Carver Jr

    2009-10-01

    Full Text Available Terrence W Carver JrThe Children’s Mercy Hospital and Clinics, Kansas City, MO, USAAbstract: Exercise-induced asthma/exercise-induced bronchospasm (EIA/EIB is a prevalent and clinically important disease affecting young children through older adulthood. These terms are often used interchangeably and the differences are not clearly defined in the literature. The pathogenesis of EIA/EIB may be different in those with persistent asthma compared to those with exercise-induced symptoms only. The natural history of EIA is unclear and may be different for elite athletes. Leukotriene biology has helped the understanding of EIB. The type and intensity of exercise are important factors for EIB. Exercise participation is necessary for proper development and control of EIA is recommended. Symptoms of EIB should be confirmed by proper testing. Biologic markers may also be helpful in diagnosis. Not all exercise symptoms are from EIB. Many medication and nonpharmacologic treatments are available. Asthma education is an important component of managing EIA. Many medications have been tested and the comparisons are complicated. Montelukast is a US Food and Drug Administration-approved asthma and EIB controller and has a number of potential advantages to other asthma medications including short onset of action, ease of use, and lack of tolerance. Not all patients improve with montelukast and rescue medication should be available.Keywords: exercise, asthma, montelukast, Singulair, bronchospasm, leukotrienes

  6. Asthma and exercise-induced respiratory symptoms in the athlete: new insights.

    Science.gov (United States)

    Boulet, Louis-Philippe; Turmel, Julie; Côté, Andréanne

    2017-01-01

    Asthma and exercise-induced bronchoconstriction (EIB) are common in the athlete and can interfere with sport performances. In this review, we report recent findings on the prevalence, diagnosis and evaluation of these conditions, in addition to specific issues regarding their treatment and antidoping regulations. Recent studies confirmed the high prevalence of exercise-induced respiratory symptoms, asthma and EIB, in athletes and showed that these conditions are still underdiagnosed and undertreated. Recent studies highlight the suboptimal use of asthma medication in asthmatic and allergic athletes. Regarding the diagnosis and treatment, questions about the role and criteria for positivity of eucapnic voluntary hyperpnea test were raised. It was confirmed that there is a subgroup of athletes with poor response to asthma medication. Finally, regarding antidoping regulations, new methods and changes in criteria for urinary bronchodilator thresholds were suggested. Recent publications confirm that exercise-induced respiratory symptoms, asthma and EIB are common in athletes but often unrecognized and not optimally or successfully treated. It was suggested that current criteria for diagnostic bronchoprovocation test responses could be reassessed, as well as antidoping criteria for β2-agonists urinary levels. There is a need for more research on prevention of airways dysfunction in athletes, identification of different asthma phenotypes and the benefits of standard asthma medication in this population.

  7. Acute exercise induces biphasic increase in respiratory mRNA in skeletal muscle

    International Nuclear Information System (INIS)

    Ikeda, Shin-ichi; Kizaki, Takako; Haga, Shukoh; Ohno, Hideki; Takemasa, Tohru

    2008-01-01

    Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) promotes the expression of oxidative enzymes in skeletal muscle. We hypothesized that activation of the p38 MAPK (mitogen-activated protein kinase) in response to exercise was associated with exercise-induced PGC-1α and respiratory enzymes expression and aimed to demonstrate this under the physiological level. We subjected mice to a single bout of treadmill running and found that the exercise induced a biphasic increase in the expression of respiratory enzymes mRNA. The second phase of the increase was accompanied by an increase in PGC-1α protein, but the other was not. Administration of SB203580 (SB), an inhibitor of p38 MAPK, suppressed the increase in PGC-1α expression and respiratory enzymes mRNA in both phases. These data suggest that p38 MAPK is associated with the exercise-induced expression of PGC-1α and biphasic increase in respiratory enzyme mRNAs in mouse skeletal muscle under physiological conditions

  8. Interaction of N-terminal peptide analogues of the Na+,K+-ATPase with membranes.

    Science.gov (United States)

    Nguyen, Khoa; Garcia, Alvaro; Sani, Marc-Antoine; Diaz, Dil; Dubey, Vikas; Clayton, Daniel; Poggetto, Giovanni Dal; Cornelius, Flemming; Payne, Richard J; Separovic, Frances; Khandelia, Himanshu; Clarke, Ronald J

    2018-03-06

    The Na + ,K + -ATPase, which is present in the plasma membrane of all animal cells, plays a crucial role in maintaining the Na + and K + electrochemical potential gradients across the membrane. Recent studies have suggested that the N-terminus of the protein's catalytic α-subunit is involved in an electrostatic interaction with the surrounding membrane, which controls the protein's conformational equilibrium. However, because the N-terminus could not yet be resolved in any X-ray crystal structures, little information about this interaction is so far available. In measurements utilising poly-l-lysine as a model of the protein's lysine-rich N-terminus and using lipid vesicles of defined composition, here we have identified the most likely origin of the interaction as one between positively charged lysine residues of the N-terminus and negatively charged headgroups of phospholipids (notably phosphatidylserine) in the surrounding membrane. Furthermore, to isolate which segments of the N-terminus could be involved in membrane binding, we chemically synthesized N-terminal fragments of various lengths. Based on a combination of results from RH421 UV/visible absorbance measurements and solid-state 31 P and 2 H NMR using these N-terminal fragments as well as MD simulations it appears that the membrane interaction arises from lysine residues prior to the conserved LKKE motif of the N-terminus. The MD simulations indicate that the strength of the interaction varies significantly between different enzyme conformations. Copyright © 2018. Published by Elsevier B.V.

  9. Antimicrobial activity of human prion protein is mediated by its N-terminal region.

    Directory of Open Access Journals (Sweden)

    Mukesh Pasupuleti

    Full Text Available BACKGROUND: Cellular prion-related protein (PrP(c is a cell-surface protein that is ubiquitously expressed in the human body. The multifunctionality of PrP(c, and presence of an exposed cationic and heparin-binding N-terminus, a feature characterizing many antimicrobial peptides, made us hypothesize that PrP(c could exert antimicrobial activity. METHODOLOGY AND PRINCIPAL FINDINGS: Intact recombinant PrP exerted antibacterial and antifungal effects at normal and low pH. Studies employing recombinant PrP and N- and C-terminally truncated variants, as well as overlapping peptide 20mers, demonstrated that the antimicrobial activity is mediated by the unstructured N-terminal part of the protein. Synthetic peptides of the N-terminus of PrP killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the "classical" human antimicrobial peptide LL-37. In contrast to LL-37, however, no marked helix induction was detected for the PrP-derived peptides in presence of negatively charged (bacteria-mimicking liposomes. PrP furthermore showed an inducible expression during wounding of human skin ex vivo and in vivo, as well as stimulation of keratinocytes with TGF-alpha in vitro. CONCLUSIONS: The demonstration of an antimicrobial activity of PrP, localisation of its activity to the N-terminal and heparin-binding region, combined with results showing an increased expression of PrP during wounding, indicate that PrPs could have a previously undisclosed role in host defense.

  10. Powdery mildew fungal effector candidates share N-terminal Y/F/WxC-motif

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    Emmersen Jeppe

    2010-05-01

    Full Text Available Abstract Background Powdery mildew and rust fungi are widespread, serious pathogens that depend on developing haustoria in the living plant cells. Haustoria are separated from the host cytoplasm by a plant cell-derived extrahaustorial membrane. They secrete effector proteins, some of which are subsequently transferred across this membrane to the plant cell to suppress defense. Results In a cDNA library from barley epidermis containing powdery mildew haustoria, two-thirds of the sequenced ESTs were fungal and represented ~3,000 genes. Many of the most highly expressed genes encoded small proteins with N-terminal signal peptides. While these proteins are novel and poorly related, they do share a three-amino acid motif, which we named "Y/F/WxC", in the N-terminal of the mature proteins. The first amino acid of this motif is aromatic: tyrosine, phenylalanine or tryptophan, and the last is always cysteine. In total, we identified 107 such proteins, for which the ESTs represent 19% of the fungal clones in our library, suggesting fundamental roles in haustoria function. While overall sequence similarity between the powdery mildew Y/F/WxC-proteins is low, they do have a highly similar exon-intron structure, suggesting they have a common origin. Interestingly, searches of public fungal genome and EST databases revealed that haustoria-producing rust fungi also encode large numbers of novel, short proteins with signal peptides and the Y/F/WxC-motif. No significant numbers of such proteins were identified from genome and EST sequences from either fungi which do not produce haustoria or from haustoria-producing Oomycetes. Conclusion In total, we identified 107, 178 and 57 such Y/F/WxC-proteins from the barley powdery mildew, the wheat stem rust and the wheat leaf rust fungi, respectively. All together, our findings suggest the Y/F/WxC-proteins to be a new class of effectors from haustoria-producing pathogenic fungi.

  11. Unusual chemical properties of N-terminal histidine residues of glucagon and vasoactive intestinal peptide

    International Nuclear Information System (INIS)

    Hefford, M.A.; Evans, R.M.; Oda, G.; Kaplan, H.

    1985-01-01

    An N-terminal histidine residue of a protein or peptide has two functional groups, viz., an alpha-amino group and an imidazole group. A new procedure, based on the competitive labeling approach described by Duggleby and Kaplan has been developed by which the chemical reactivity of each functional group in such a residue can be determined as a function of pH. Only very small amounts of material are required, which makes it possible to determine the chemical properties in dilute solution or in proteins and polypeptides that can be obtained in only minute quantities. With this approach, the reactivity of the alpha-amino group of histidylglycine toward 1-fluoro-2,4-dinitrobenzene gave an apparent pK /sub a/ value of 7.64 +/- 0.07 at 37 degrees C, in good agreement with a value of 7.69 +/- 0.02 obtained by acid-base titration. However, the reactivity of the imidazole function gave an apparent pK /sub a/ value of 7.16 +/- 0.07 as compared to the pK /sub a/ value of 5.85 +/- 0.01 obtained by acid-base titration. Similarly, in glucagon and vasoactive intestinal peptide (VIP), apparent pKa values of 7.60 +/- 0.04 and 7.88 +/- 0.18, respectively, were obtained for the alpha-amino of their N-terminal histidine, and pKa values of 7.43 +/- 0.09 and 7.59 +/- 0.18 were obtained for the imidazole function

  12. NMR and structural data for Connexin 32 and Connexin 26 N-terminal peptides

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    Yuksel Batir

    2016-12-01

    Full Text Available In this article we present 1H and 13C chemical shift assignments, secondary structural propensity data and normalized temperature coefficient data for N-terminal peptides of Connexin 26 (Cx26, Cx26G12R and Cx32G12R mutants seen in syndromic deafness and Charcot Marie Tooth Disease respectively, published in “Structural Studies of N-Terminal Mutants of Connexin 26 and Connexin 32 Using 1H NMR Spectroscopy” (Y. Batir, T.A. Bargiello, T.L. Dowd, 2016 [1]. The mutation G12R affects the structure of both Cx26 and Cx32 peptides differently. We present data from secondary structure propensity chemical shift analysis which calculates a secondary structure propensity (SSP score for both disordered or folded peptides and proteins using the difference between the 13C secondary chemical shifts of the Cα and Cβ protons. This data supplements the calculated NMR structures from NOESY data [1]. We present and compare the SSP data for the Cx26 vs Cx26G12R peptides and the Cx32 and Cx32G12R peptides. In addition, we present plots of temperature coefficients obtained for Cx26, Cx26G12R and Cx32G12R peptides collected previously [1] and normalized to their random coil temperature coefficients, “Random coil 1H chemical shifts obtained as a function of temperature and trifluoroethanol concentration for the peptide series GGXGG” (G. Merutka, H.J. Dyson, P.E. Wright, 1995 [2]. Reductions in these normalized temperature coefficients are directly observable for residues in different segments of the peptide and this data informs on solvent accessibility of the NH protons and NH protons which may be more constrained due to the formation of H bonds.

  13. The ability of NT-proBNP to detect chronic heart failure and predict all-cause mortality is higher in elderly Chinese coronary artery disease patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Fu S

    2013-04-01

    Full Text Available Shihui Fu, Leiming Luo, Ping Ye, Shuangyan Yi, Yuan Liu, Bing Zhu, Liang Wang, Tiehui Xiao, Yongyi Bai Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, People's Republic of China Objective: To analyze the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP and renal function, and compare the ability and cut-off thresholds of NT-proBNP to detect chronic heart failure (CHF and predict mortality in elderly Chinese coronary artery disease (CAD patients with and without chronic kidney disease (CKD. Methods: The study included 999 CAD patients older than 60 years. The endpoint was all-cause mortality over a mean follow-up period of 417 days. Results: The median age was 86 years (range: 60–104 years, and the median NT-proBNP level was 409.8 pg/mL. CKD was present in 358 patients. Three hundred and six patients were positive for CHF. One hundred and ten CKD patients and 105 non-CKD patients died. Not only CKD, but also estimated glomerular filtration rate independently affected NT-proBNP. NT-proBNP detected CHF with a cut-off value of 298.4 pg/mL in non-CKD patients and a cut-off value of 435.7 pg/mL in CKD patients. NT-proBNP predicted death with a cut-off value of 369.5 pg/mL in non-CKD patients and a cut-off value of 2584.1 pg/mL in CKD patients. The NT-proBNP level was significantly related to the prevalence of CHF and all-cause mortality in CAD patients with and without CKD; this effect persisted after adjustment. The crude and multiple adjusted hazard ratios of NT-proBNP to detect CHF and predict mortality were significantly higher in patients with CKD compared with the remainder of the population. The addition of NT-proBNP to the three-variable and six-variable models generated a significant increase in the C-statistic. Conclusion: Amongst elderly Chinese CAD patients, there was an independently inverse association between NT-proBNP and renal function. With the higher cutoff points, NT

  14. Different impact of aortic regurgitation assessed by aortic root angiography after transcatheter aortic valve implantation according to baseline left ventricular ejection fraction and N-terminal pro-B-type natriuretic peptide.

    Science.gov (United States)

    Kaneko, Hidehiro; Hoelschermann, Frank; Schau, Thomas; Tambor, Grit; Neuss, Michael; Butter, Christian

    2017-05-31

    Transcatheter aortic valve implantation (TAVI) is an alternative therapeutic option for severe aortic stenosis. Aortic regurgitation (AR) is commonly observed after TAVI and increases the mortality rate. We hypothesized that the influence of significant AR, defined as that more severe than mild AR, on survival rate after TAVI might differ according to the baseline left ventricular ejection fraction (LVEF) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) level. We categorized 856 patients who underwent transfemoral TAVI into 2 groups according to their baseline LVEF (5000 pg/mL). Significant AR was observed in 92 patients (11%). Among patients with significant AR, the proportion of patients with CoreValve/EvolutR implantation was higher than that of patients with SAPIEN XT/3 implantation. Kaplan-Meier curves and the log-rank test showed that significant AR was not associated with 1-year mortality in patients with LVEF ≥40% and those with NT-pro BNP level ≤5000 pg/mL. On the other hand, it was significantly associated with a higher 1-year mortality in patients with LVEF 5000 pg/mL (p = 0.011). Similarly, multivariate Cox regression analysis showed that the presence of AR was significantly associated with a higher 1-year mortality in patients with LVEF 5000 pg/mL (p = 0.004, HR = 3.221). However, AR was not significantly associated with a higher 1-year mortality in patients with LVEF ≥40% and NT-pro BNP level ≤5000 pg/mL. Thus, the impact of significant AR on mortality after TAVI seems to be considerable in patients with reduced LVEF or high NT-pro BNP levels, but not those with preserved LVEF or low NT-pro BNP levels, suggesting that the influence of AR differs depending on the baseline LVEF and NT-pro BNP level.

  15. Duration of action of formoterol and salbutamol dry-powder inhalation in prevention of exercise-induced asthma in children

    DEFF Research Database (Denmark)

    Daugbjerg, Peer Schrøder; Nielsen, K G; Skov, M

    1996-01-01

    The aim of this study was to evaluate the effect and tolerability of formoterol 12 micrograms on exercise-induced asthma in children for 12 h as compared to the effect of salbutamol 400 micrograms and placebo. The drugs were inhaled as dry powder from a flow-dependent metered-dose inhaler (DP....... Formoterol 12 micrograms administered as dry powder offers significantly better protection against exercise-induced asthma after 3 and 12 h as compared to salbutamol 400 micrograms and placebo....

  16. Correlation between spina bifida manifesta in fetal rats and c-Jun N-terminal kinase signaling★

    Science.gov (United States)

    Ma, Yinghuan; Bao, Yongxin; Li, Chenghao; Jiao, Fubin; Xin, Hongjie; Yuan, Zhengwei

    2012-01-01

    Fetal rat models with neural tube defects were established by injection with retinoic acid at 10 days after conception. The immunofluorescence assay and western blot analysis showed that the number of caspase-3 positive cells in myeloid tissues for spina bifida manifesta was increased. There was also increased phosphorylation of c-Jun N-terminal kinase, a member of the mitogen activated protein kinase family. The c-Jun N-terminal kinase phosphorylation level was positively correlated with caspase-3 expression in myeloid tissues for spina bifida manifesta. Experimental findings indicate that abnormal apoptosis is involved in retinoic acid-induced dominant spina bifida formation in fetal rats, and may be associated with the c-Jun N-terminal kinase signal transduction pathway. PMID:25337099

  17. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    Predictive studies suggest that the known sequences of the N-terminal segment of surfactant protein SP-C from animal species have an intrinsic tendency to form beta-turns, but there are important differences on the probable location of these motifs in different SP-C species. Our hypothesis...... is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides corresponding to the 13-residue N-terminal sequence of porcine and canine SP......-C, and studied their structural behaviour in solution and in phospholipid bilayers and monolayers. In these peptides, leucine at position 1 of both sequences has been replaced by tryptophan in order to allow their study by fluorescence spectroscopy. Far-u.v. circular dichroism spectra of the peptides in aqueous...

  18. Prokaryotic Expression and Purification of Human TLE1 N-terminal Q Domain Fragment and Production of its Polyclonal Antibody

    Directory of Open Access Journals (Sweden)

    Su WANG

    2010-11-01

    Full Text Available Background and objective TLE1 is an important protein in regulating Wnt, Notch and EGFR signaling pathways. The TLE1 N-terminal Q domain regulates the pathways by mediating its oligomerization and interaction with LEF1. The aim of this study is to construct the human TLE1 N-terminal Q domain fragment in prokaryotic expression system, express and purify protein TLE1 N-terminal Q domain and prepare its polyclonal antibody. Methods The sequence of TLE1 N-terminal Q domain obtained by PCR from human lung adenocarcinoma cDNA, was cloned into the prokaryotic expression vector pGEX-4T-1 containing Glutathione S-transferase (GST. Vector pGEX-4T1-TLE1-Q was transformed into E.coli BL21 condon plus. The GST-TLE1-Q(1-136 fusion protein was induced by IPTG, digested by Thrombin, purified with glutathione-sepharose beads and FPLC, identified by SDS-PAGE. Then rabbits were immunized with the purified protein TLE1-Q(1-136 for obtaining the antiserum. The titers and specificity of antibodies were measured by ELISA and Western blot. Results The PCR identification and the sequencing of recombinant plasmid demonstrated that vector pGEX-4T1-TLE1-Q was successfully constructed. The SDS-PAGE shows target protein (14 000 Da is the interest protein TLE1-Q(1-136. The TLE1 N-terminal Q domain fragment TLE1-Q(1-136 and its polyclonal antibody have been acquired, with an antibody titer of 1:20 000. Conclusion Expression vector pGEX-4T1-TLE1-Q is correctly constructed. The TLE1 N-terminal Q domain fragment TLE1-Q(1-136 and its polyclonal antibody have been acquired. These work established the foundation for further biological study between TLE1 and lung cancers.

  19. Redox-linked Gating of Nucleotide Binding by the N-terminal Domain of Adenosine 5′-Phosphosulfate Kinase*

    Science.gov (United States)

    Ravilious, Geoffrey E.; Westfall, Corey S.; Jez, Joseph M.

    2013-01-01

    Adenosine 5′-phosphosulfate kinase (APSK) catalyzes the phosphorylation of adenosine 5′-phosphosulfate (APS) to 3′-phosphoadenosine-5′-phosphosulfate (PAPS). Crystallographic studies of APSK from Arabidopsis thaliana revealed the presence of a regulatory intersubunit disulfide bond (Cys86–Cys119). The reduced enzyme displayed improved catalytic efficiency and decreased effectiveness of substrate inhibition by APS compared with the oxidized form. Here we examine the effect of disulfide formation and the role of the N-terminal domain on nucleotide binding using isothermal titration calorimetry (ITC) and steady-state kinetics. Formation of the disulfide bond in A. thaliana APSK (AtAPSK) inverts the binding affinities at the ATP/ADP and APS/PAPS sites from those observed in the reduced enzyme, consistent with initial binding of APS as inhibitory, and suggests a role for the N-terminal domain in guiding nucleotide binding order. To test this, an N-terminal truncation variant (AtAPSKΔ96) was generated. The resulting protein was completely insensitive to substrate inhibition by APS. ITC analysis of AtAPSKΔ96 showed decreased affinity for APS binding, although the N-terminal domain does not directly interact with this ligand. Moreover, AtAPSKΔ96 displayed reduced affinity for ADP, which corresponds to a loss of substrate inhibition by formation of an E·ADP·APS dead end complex. Examination of the AtAPSK crystal structure suggested Arg93 as important for positioning of the N-terminal domain. ITC and kinetic analysis of the R93A mutant also showed a complete loss of substrate inhibition and altered nucleotide binding affinities, which mimics the effect of the N-terminal deletion. These results show how thiol-linked changes in AtAPSK alter the energetics of binding equilibria to control its activity. PMID:23322773

  20. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides corresponding to the 13-residue N-terminal sequence of porcine and canine SP...... the packing of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) monolayers, the effects being always higher in anionic than in zwitterionic lipids, and also substantially higher in films containing canine peptide in comparison to porcine peptide. Acylation of cysteines at the N...

  1. Altering the N-terminal arms of the polymerase manager protein UmuD modulates protein interactions.

    Directory of Open Access Journals (Sweden)

    David A Murison

    Full Text Available Escherichia coli cells that are exposed to DNA damaging agents invoke the SOS response that involves expression of the umuD gene products, along with more than 50 other genes. Full-length UmuD is expressed as a 139-amino-acid protein, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The N-terminal arms of UmuD are dynamic and contain recognition sites for multiple partner proteins. Cleavage of UmuD to UmuD' dramatically affects the function of the protein and activates UmuC for translesion synthesis (TLS by forming DNA Polymerase V. To probe the roles of the N-terminal arms in the cellular functions of the umuD gene products, we constructed additional N-terminal truncated versions of UmuD: UmuD 8 (UmuD Δ1-7 and UmuD 18 (UmuD Δ1-17. We found that the loss of just the N-terminal seven (7 amino acids of UmuD results in changes in conformation of the N-terminal arms, as determined by electron paramagnetic resonance spectroscopy with site-directed spin labeling. UmuD 8 is cleaved as efficiently as full-length UmuD in vitro and in vivo, but expression of a plasmid-borne non-cleavable variant of UmuD 8 causes hypersensitivity to UV irradiation, which we determined is the result of a copy-number effect. UmuD 18 does not cleave to form UmuD', but confers resistance to UV radiation. Moreover, removal of the N-terminal seven residues of UmuD maintained its interactions with the alpha polymerase subunit of DNA polymerase III as well as its ability to disrupt interactions between alpha and the beta processivity clamp, whereas deletion of the N-terminal 17 residues resulted in decreases in binding to alpha and in the ability to disrupt the alpha-beta interaction. We find that UmuD 8 mimics full-length UmuD in many respects, whereas UmuD 18 lacks a number of functions characteristic of UmuD.

  2. NT-proBNP is superior to BNP for predicting first cardiovascular events in the general population: the Heinz Nixdorf Recall Study.

    Science.gov (United States)

    Kara, Kaffer; Lehmann, Nils; Neumann, Till; Kälsch, Hagen; Möhlenkamp, Stefan; Dykun, Iryna; Broecker-Preuss, Martina; Pundt, Noreen; Moebus, Susanne; Jöckel, Karl-Heinz; Erbel, Raimund; Mahabadi, Amir A

    2015-03-15

    B-type natriuretic peptide (BNP) as well as N-terminal-proBNP (NT-proBNP) are associated with cardiac events in the general population. Yet, data from the general population comparing both peptides for their prognostic value is lacking. Participants from the population-based Heinz-Nixdorf-Recall-study without cardiovascular diseases were included. Associations of BNP and NT-proBNP with incident cardiovascular events (incident myocardial infarction, stroke, or cardiovascular death) were assessed using Cox regression; prognostic value was addressed using Harrell's c statistic. From overall 3589 subjects (mean age: 59.3 ± 7.7 yrs, 52.5% female), 235 subjects developed a cardiovascular event during 8.9 ± 2.2 yrs of follow-up. In regression analysis both natriuretic peptides were associated with incident cardiovascular events, independent of traditional risk factors (hazard ratio (HR) per unit increase on log-scale (95% CI): NT-proBNP: 1.60 (1.39; 1.84); BNP: 1.37 (1.19; 1.58), p<0.0001 respectively). Specifically looking at subjects <60 yrs only NT-proBNP, was linked with events (HR (95% CI): 1.59 (1.19; 2.13) for NT-proBNP, p=0.0019; HR: 1.25 (0.94; 1.65) for BNP, p=0.12, after adjustment for age and gender). Similar results were observed for females (HR (95% CI) 1.65 (1.28; 2.12), p=0.0001 for NT-proBNP, and 1.24 (0.96; 1.61), p=0.10 for BNP after adjustment for age). Adding NT-proBNP/BNP to traditional risk factors increased the prognostic value, with effects being stronger for NT-proBNP (Harrell's c, 0.724 to 0.741, p=0.034) as compared to BNP (0.724 to 0.732, p=0.20). Both, NT-proBNP and BNP are associated with future cardiovascular events in the general population. However, when both are available, NT-proBNP seems to be superior due to its higher prognostic value, especially in younger subjects and females. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. The Effect of Omega-3 Polyunsaturated Fatty Acids on N-Terminal Pro-Brain Natriuretic Peptide and Lipids Concentration in Patients With Type 2 Diabetes Mellitus and Cardiovascular Autonomic Neuropathy

    Directory of Open Access Journals (Sweden)

    Serhiyenko Victoria

    2014-06-01

    Full Text Available Background and Aims: Cardiac autonomic neuropathy (CAN in type 2 diabetes mellitus (T2DM is one of the independent risk factor for cardiovascular mortality. The aim of the study was to analyze the effect of long-chain w-3 polyunsaturated fatty acids (w-3 PUFA on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP and on some lipid profile parameters in patients with T2DM and CAN. Material and Methods: 36 patients with T2DM and verified CAN were divided into 2 groups. The first group received traditional hypoglycemic therapy (n = 15, control for three months; patients in group 2 (n = 21 received in addition 1 g/day of the long-chain w-3 PUFA for three months. Results: Prescription of the w-3 PUFA to the patients with T2DM and СAN was accompanied by a statistically significant decrease of NT-proBNP level and led to significantly positive changes in the high density lipoprotein cholesterol and triglycerides levels in the blood. Conclusions: Obtained results suggest that the efficacy of w-3 PUFA is the result of a direct effect of the pharmacological agent on the investigated indexes

  4. Vitamins C and E for asthma and exercise-induced bronchoconstriction.

    Science.gov (United States)

    Wilkinson, Mark; Hart, Anna; Milan, Stephen J; Sugumar, Karnam

    2014-06-17

    The association between dietary antioxidants and asthma or exercise-induced bronchoconstriction (EIB) is not fully understood. Vitamin C and vitamin E are natural antioxidants that are predominantly present in fruits and vegetables; inadequate vitamin E intake is associated with airway inflammation. It has been postulated that the combination may be more beneficial than either single antioxidant for people with asthma and exercise-induced bronchoconstriction. To assess the effects of supplementation of vitamins C and E versus placebo (or no vitamin C and E supplementation) on exacerbations and health-related quality of life (HRQL) in adults and children with chronic asthma. To also examine the potential effects of vitamins C and E on exercise-induced bronchoconstriction in people with asthma and in people without a diagnosis of asthma who experience symptoms only on exercise. Trials were identified from the Cochrane Airways Review Group Specialised Register and from trial registry websites. Searches were conducted in September 2013. We included randomised controlled trials of adults and children with a diagnosis of asthma. We separately considered trials in which participants had received a diagnosis of exercise-induced bronchoconstriction (or exercise-induced asthma). Trials comparing vitamin C and E supplementation versus placebo were included. We included trials in which asthma management for treatment and control groups included similar background therapy. Short-term use of vitamins C and E at the time of exacerbation or for cold symptoms in people with asthma is outside the scope of this review. Two review authors independently screened the titles and abstracts of potential studies and subsequently screened full-text study reports for inclusion. We used standard methods as expected by The Cochrane Collaboration. It was not possible to aggregate the five included studies (214 participants). Four studies (206 participants) addressed the question of whether

  5. X-ray diffraction studies on merohedrally twinned Δ1–62NtNBCe1-A crystals of the sodium/bicarbonate cotransporter

    International Nuclear Information System (INIS)

    Gill, Harindarpal S.; Dutcher, Lauren; Boron, Walter F.; Patel, Samir; Guay-Woodford, Lisa M.

    2013-01-01

    A truncated mutant missing the first 62 residues of the N-terminal, cytoplasmic domain of the sodium-bicarbonate NBCe1-A cotransporter crystallizes in space group P3 1 with pseudo-P3 1 21 symmetry and a hemihedral twin fraction of 33.0%. Twinned fractions and twin-pair statistics over binned resolutions confirm that the calculated twin fraction is associated with hemihedral twinning and not to non-crystallographic symmetry. NBCe1-A membrane-embedded macromolecules that cotransport sodium and bicarbonate ions across the bilayer serve to maintain acid–base homeostasis throughout the body. Defects result in a number of renal and eye disorders, including type-II renal tubular acidosis and cataracts. Here, crystals of a human truncated mutant of the cytoplasmic N-terminal domain of NBCe1 (Δ1–62NtNBCe1-A) are reported that diffract X-rays to 2.4 Å resolution. The crystal symmetry of Δ1–62NtNBCe1-A is of space group P3 1 with pseudo-P3 1 21 symmetry and it has a hemihedral twin fraction of 33.0%. The crystals may provide insight into the pathogenic processes observed in a subset of patients with truncating and point mutations in the gene encoding NBCe1

  6. Effects of right ventricular dysfunction on exercise capacity and quality of life and associations with serum NT-proBNP levels in COPD: an observational study.

    Science.gov (United States)

    Ozdemirel, Tuğce Sahin; Ulaşli, Sevinç Sarinç; Yetiş, Begüm; Karaçağlar, Emir; Bayraktar, Nilüfer; Ulubay, Gaye

    2014-06-01

    During the course of chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH) and right ventricular (RV) failure may develop due to elevated afterload of the RV. In those patients, exercise capacity is reduced due to pulmonary and cardiac limitations. We investigated relationships between serum N-terminal of proB-type natriuretic peptide (NT-proBNP) and RV functions with exercise capacity and quality of life in patients COPD. An observational case-control study was conducted. We enrolled 31 moderate and severe COPD patients, and 20 subjects without chronic diseases as control group. Parameters reflecting the right ventricular diastolic and systolic functions by echocardiography along with serum NT-proBNP levels were assessed. Cardiopulmonary exercise testing and Short Form-36 (SF-36) were applied. Serum NT-proBNP levels were higher in COPD patients than control group (p=0.003). Serum NT-proBNP level was found to be related with pulmonary arterial pressure. Serum NT-proBNP levels were negatively correlated with anaerobic threshold oxygen uptake (AT VO2) and peak oxygen uptake (PVO2) values. Early ventricular filling velocity (Em) was lower in COPD patients. Em wave was significantly correlated with O2 pulse. There was a positive relationship between tricuspid E/A ratio and VO2 value at AT. SF-36 domains of physical functioning, general health and role limitation due to physical disorder were significantly correlated with AT VO2, PVO2 and O2 pulse. Exercise limitation may be predicted by assessment of right ventricule functions and NT-proBNP levels and exercise limitation impairs quality of life in COPD patients.

  7. PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial.

    Science.gov (United States)

    Huelsmann, Martin; Neuhold, Stephanie; Resl, Michael; Strunk, Guido; Brath, Helmut; Francesconi, Claudia; Adlbrecht, Christopher; Prager, Rudolf; Luger, Anton; Pacher, Richard; Clodi, Martin

    2013-10-08

    The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP). Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context. A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years. At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment

    Directory of Open Access Journals (Sweden)

    Kabat David

    2007-08-01

    Full Text Available Abstract Background HIV-1 envelope glycoprotein (Env induces membrane fusion as a result of sequential binding to CD4 and chemokine receptors (CCR5 or CXCR4. The critical determinants of CCR5 coreceptor function are the N-terminal domain (Nt and the second extracellular loop. However, mutations in gp120 adapt HIV-1 to grow on cells expressing the N-terminally truncated CCR5(Δ18 (Platt et al., J. Virol. 2005, 79: 4357–68. Results We have functionally characterized the adapted Env (designated Env(NYP using a quantitative cell-cell fusion assay. The rate of fusion with target cells expressing wild-type CCR5 and the resistance to fusion inhibitors was virtually identical for wild-type Env and Env(NYP, implying that the coreceptor affinity had not increased as a result of adaptation. In contrast, Env(NYP-induced fusion with cells expressing CCR5(Δ18 occurred at a slower rate and was extremely sensitive to the CCR5 binding inhibitor, Sch-C. Resistance to Sch-C drastically increased after pre-incubation of Env(NYP- and CCR5(Δ18-expressing cells at a temperature that was not permissive to fusion. This indicates that ternary Env(NYP-CD4-CCR5(Δ18 complexes accumulate at sub-threshold temperature and that low-affinity interactions with the truncated coreceptor are sufficient for triggering conformational changes in the gp41 of Env(NYP but not in wild-type Env. We also demonstrated that the ability of CCR5(Δ18 to support fusion and infection mediated by wild-type Env can be partially reconstituted in the presence of a synthetic sulfated peptide corresponding to the CCR5 Nt. Pre-incubation of wild-type Env- and CCR5(Δ18-expressing cells with the sulfated peptide at sub-threshold temperature markedly increased the efficiency of fusion. Conclusion We propose that, upon binding the Nt region of CCR5, wild-type Env acquires the ability to productively engage the extracellular loop(s of CCR5 – an event that triggers gp41 refolding and membrane merger

  9. NT2 derived neuronal and astrocytic network signalling.

    Directory of Open Access Journals (Sweden)

    Eric J Hill

    Full Text Available A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

  10. Secondary structure, stability and tetramerisation of recombinant Kv1.1 potassium channel cytoplasmic N-terminal fragment.

    NARCIS (Netherlands)

    Abbott, G.W.; Bloemendal, M.; van Stokkum, I.H.M.; Mercer, E.A.J.; Miller, R.T.; Sewing, S.; Wolters, M.J.J.; Pongs, O.; Srai, S.K.S.

    1997-01-01

    The recombinant N-terminal fragment (amino acids 14-162) of a tetrameric voltage-gated potassium channel (K(V)1.1) has been studied using spectroscopic techniques. Evidence is presented that it forms a tetramer in aqueous solution, whereas when solubilised in 1% Triton X-100 it remains monomeric.

  11. N-terminal amino acid sequence of Bacillus licheniformis alpha-amylase: comparison with Bacillus amyloliquefaciens and Bacillus subtilis Enzymes.

    OpenAIRE

    Kuhn, H; Fietzek, P P; Lampen, J O

    1982-01-01

    The thermostable, liquefying alpha-amylase from Bacillus licheniformis was immunologically cross-reactive with the thermolabile, liquefying alpha-amylase from Bacillus amyloliquefaciens. Their N-terminal amino acid sequences showed extensive homology with each other, but not with the saccharifying alpha-amylases of Bacillus subtilis.

  12. X-ray vs. NMR structure of N-terminal domain of delta-subunit of RNA polymerase

    Czech Academy of Sciences Publication Activity Database

    Demo, G.; Papoušková, V.; Komárek, J.; Kadeřávek, P.; Otrusinová, O.; Srb, P.; Rabatinová, Alžběta; Krásný, Libor; Žídek, L.; Sklenář, V.; Wimmerová, M.

    2014-01-01

    Roč. 187, č. 2 (2014), s. 174-186 ISSN 1047-8477 R&D Projects: GA ČR GA13-16842S Institutional support: RVO:61388971 Keywords : Protein crystallography * Nuclear magnetic resonance * N-terminal domain Subject RIV: EE - Microbiology, Virology Impact factor: 3.231, year: 2014

  13. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

  14. 1H, 13C, and 15N resonance assignments of the N-terminal domain of human TIG3.

    Science.gov (United States)

    Wang, Lei; Yu, Wenyu; Ren, Xiaobai; Lin, Jian; Jin, Changwen; Xia, Bin

    2012-10-01

    Human TIG3 protein is a member of H-REV107 protein family which belongs to the type II tumor suppressor family. TIG3 can induce apoptosis in cancer cells, and it also possesses Ca(2+)-independent phospholipase A(1/2) activity. The NMR assignments of the N-terminal domain of TIG3 are essential for its solution structure determination.

  15. Cutting edge: HLA-B27 acquires many N-terminal dibasic peptides: coupling cytosolic peptide stability to antigen presentation

    NARCIS (Netherlands)

    Herberts, Carla A.; Neijssen, Joost J.; de Haan, Jolanda; Janssen, Lennert; Drijfhout, Jan Wouter; Reits, Eric A.; Neefjes, Jacques J.

    2006-01-01

    Ag presentation by MHC class I is a highly inefficient process because cytosolic peptidases destroy most peptides after proteasomal generation. Various mechanisms shape the MHC class I peptidome. We define a new one: intracellular peptide stability. Peptides with two N-terminal basic amino acids are

  16. N-terminal propeptide of type III procollagen as a biomarker of anabolic response to recombinant human GH and testosterone

    Science.gov (United States)

    Context: Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (L...

  17. FUNCTIONAL-ANALYSIS OF THE N-TERMINAL PREPEPTIDES OF WATERMELON MITOCHONDRIAL AND GLYOXYSOMAL MALATE-DEHYDROGENASES

    NARCIS (Netherlands)

    LEHNERER, M; KEIZERGUNNIK, [No Value; VEENHUIS, M; GIETL, C

    1994-01-01

    Mitochondrial and glyoxysomal malate dehydrogenase (mMDH; gMDH; L-malate : NAD(+) oxidoreductase; EC 1.1.1.37) of watermelon (Citrullus vulgaris) cotyledons are synthesized with N-terminal cleavable presequences which are shown to specify sorting of the two proteins. The two presequences differ in

  18. Mutational analysis of the N-terminal topogenic signal of watermelon glyoxysomal malate dehydrogenase using the heterologous host Hansenula polymorpha

    NARCIS (Netherlands)

    Gietl, Christine; Faber, Klaas Nico; Klei, Ida J. van der; Veenhuis, Marten

    1994-01-01

    We have studied the significance of the N-terminal presequence of watermelon (Citrullus vulgaris) glyoxysomal malate dehydrogenase [gMDH; (S)-malate:NAD+ oxidoreductase; EC 1.1.1.37] in microbody targeting. The yeast Hansenula polymorpha was used as heterologous host for the in vivo expression of

  19. Functional and structural characterization of a synthetic peptide representing the N-terminal domain of prokaryotic pyruvate dehydrogenase

    NARCIS (Netherlands)

    Hengeveld, A.F.; Mierlo, van C.P.M.; Hooven, van den H.W.; Visser, A.J.W.G.; Kok, de A.

    2002-01-01

    A synthetic peptide (Nterm-E1p) is used to characterize the structure and function of the N-terminal region (amino acid residues 4-45) of the pyruvate dehydrogenase component (E1p) from the pyruvate dehydrogenase multienzyme complex (PDHC) from Azotobacter vinelandii. Activity and binding studies

  20. Glutamate dehydrogenase isoforms with N-terminal (His)6- or FLAG-tag retain their kinetic properties and cellular localization

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nielsen, Camilla Wendel; Hauge, Anne

    2014-01-01

    containing N-terminal (His)6 tags were successfully expressed in Sf9 cells and the recombinant proteins were isolated to ≥95 % purity in a two-step procedure involving ammonium sulfate precipitation and Ni(2+)-based immobilized metal ion affinity chromatography. To explore whether the presence of the FLAG...

  1. N-terminal amino acid sequence of Bacillus licheniformis alpha-amylase: comparison with Bacillus amyloliquefaciens and Bacillus subtilis Enzymes.

    Science.gov (United States)

    Kuhn, H; Fietzek, P P; Lampen, J O

    1982-01-01

    The thermostable, liquefying alpha-amylase from Bacillus licheniformis was immunologically cross-reactive with the thermolabile, liquefying alpha-amylase from Bacillus amyloliquefaciens. Their N-terminal amino acid sequences showed extensive homology with each other, but not with the saccharifying alpha-amylases of Bacillus subtilis. PMID:6172418

  2. N-Terminal Plasmodium vivax Merozoite Surface Protein-1, a Potential Subunit for Malaria Vivax Vaccine

    Directory of Open Access Journals (Sweden)

    Fernanda G. Versiani

    2013-01-01

    Full Text Available The human malaria is widely distributed in the Middle East, Asia, the western Pacific, and Central and South America. Plasmodium vivax started to have the attention of many researchers since it is causing diseases to millions of people and several reports of severe malaria cases have been noticed in the last few years. The lack of in vitro cultures for P. vivax represents a major delay in developing a functional malaria vaccine. One of the major candidates to antimalarial vaccine is the merozoite surface protein-1 (MSP1, which is expressed abundantly on the merozoite surface and capable of activating the host protective immunity. Studies have shown that MSP-1 possesses highly immunogenic fragments, capable of generating immune response and protection in natural infection in endemic regions. This paper shows humoral immune response to different proteins of PvMSP1 and the statement of N-terminal to be added to the list of potential candidates for malaria vivax vaccine.

  3. The outermost N-terminal region of tapasin facilitates folding of major histocompatibility complex class I

    DEFF Research Database (Denmark)

    Røder, Gustav Andreas; Geironson, Linda; Darabi, Anna

    2009-01-01

    ). Using a biochemical peptide-MHC-I-binding assay, recombinant Tpn(1-87) was found to specifically facilitate peptide-dependent folding of HLA-A*0201. Furthermore, we used Tpn(1-87) to generate a monoclonal antibody, alphaTpn(1-87)/80, specific for natural human Tpn and capable of cellular staining of ER......Tapasin (Tpn) is an ER chaperone that is uniquely dedicated to MHC-I biosynthesis. It binds MHC-I molecules, integrates them into peptide-loading complexes, and exerts quality control of the bound peptides; only when an "optimal peptide" is bound will the MHC-I be released and exported to the cell...... surface for presentation to T cells. The exact mechanisms of Tpn quality control and the criteria for being an optimal peptide are still unknown. Here, we have generated a recombinant fragment of human Tpn, Tpn(1-87) (representing the 87 N-terminal and ER-luminal amino acids of the mature Tpn protein...

  4. Solution structure of Atg8 reveals conformational polymorphism of the N-terminal domain

    Energy Technology Data Exchange (ETDEWEB)

    Schwarten, Melanie, E-mail: m.schwarten@fz-juelich.de [Institut fuer Strukturbiologie und Biophysik, ISB-3, Forschungszentrum Juelich, 52425 Juelich (Germany); Institut fuer Physikalische Biologie und BMFZ, Heinrich-Heine-Universitaet Duesseldorf, 40225 Duesseldorf (Germany); Stoldt, Matthias, E-mail: m.stoldt@fz-juelich.de [Institut fuer Strukturbiologie und Biophysik, ISB-3, Forschungszentrum Juelich, 52425 Juelich (Germany); Institut fuer Physikalische Biologie und BMFZ, Heinrich-Heine-Universitaet Duesseldorf, 40225 Duesseldorf (Germany); Mohrlueder, Jeannine, E-mail: j.mohrlueder@fz-juelich.de [Institut fuer Strukturbiologie und Biophysik, ISB-3, Forschungszentrum Juelich, 52425 Juelich (Germany); Willbold, Dieter, E-mail: dieter.willbold@uni-duesseldorf.de [Institut fuer Strukturbiologie und Biophysik, ISB-3, Forschungszentrum Juelich, 52425 Juelich (Germany); Institut fuer Physikalische Biologie und BMFZ, Heinrich-Heine-Universitaet Duesseldorf, 40225 Duesseldorf (Germany)

    2010-05-07

    During autophagy a crescent shaped like membrane is formed, which engulfs the material that is to be degraded. This membrane grows further until its edges fuse to form the double membrane covered autophagosome. Atg8 is a protein, which is required for this initial step of autophagy. Therefore, a multistage conjugation process of newly synthesized Atg8 to phosphatidylethanolamine is of critical importance. Here we present the high resolution structure of unprocessed Atg8 determined by nuclear magnetic resonance spectroscopy. Its C-terminal subdomain shows a well-defined ubiquitin-like fold with slightly elevated mobility in the pico- to nanosecond timescale as determined by heteronuclear NOE data. In comparison to unprocessed Atg8, cleaved Atg8{sup G116} shows a decreased mobility behaviour. The N-terminal domain adopts different conformations within the micro- to millisecond timescale. The possible biological relevance of the differences in dynamic behaviours between both subdomains as well as between the cleaved and uncleaved forms is discussed.

  5. N-Terminal-Based Targeted, Inducible Protein Degradation in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Karthik Sekar

    Full Text Available Dynamically altering protein concentration is a central activity in synthetic biology. While many tools are available to modulate protein concentration by altering protein synthesis rate, methods for decreasing protein concentration by inactivation or degradation rate are just being realized. Altering protein synthesis rates can quickly increase the concentration of a protein but not decrease, as residual protein will remain for a while. Inducible, targeted protein degradation is an attractive option and some tools have been introduced for higher organisms and bacteria. Current bacterial tools rely on C-terminal fusions, so we have developed an N-terminal fusion (Ntag strategy to increase the possible proteins that can be targeted. We demonstrate Ntag dependent degradation of mCherry and beta-galactosidase and reconfigure the Ntag system to perform dynamic, exogenously inducible degradation of a targeted protein and complement protein depletion by traditional synthesis repression. Model driven analysis that focused on rates, rather than concentrations, was critical to understanding and engineering the system. We expect this tool and our model to enable inducible protein degradation use particularly in metabolic engineering, biological study of essential proteins, and protein circuits.

  6. NMR structure of the N-terminal domain of the replication initiator protein DnaA

    Energy Technology Data Exchange (ETDEWEB)

    Wemmer, David E.; Lowery, Thomas J.; Pelton, Jeffrey G.; Chandonia, John-Marc; Kim, Rosalind; Yokota, Hisao; Wemmer, David E.

    2007-08-07

    DnaA is an essential component in the initiation of bacterial chromosomal replication. DnaA binds to a series of 9 base pair repeats leading to oligomerization, recruitment of the DnaBC helicase, and the assembly of the replication fork machinery. The structure of the N-terminal domain (residues 1-100) of DnaA from Mycoplasma genitalium was determined by NMR spectroscopy. The backbone r.m.s.d. for the first 86 residues was 0.6 +/- 0.2 Angstrom based on 742 NOE, 50 hydrogen bond, 46 backbone angle, and 88 residual dipolar coupling restraints. Ultracentrifugation studies revealed that the domain is monomeric in solution. Features on the protein surface include a hydrophobic cleft flanked by several negative residues on one side, and positive residues on the other. A negatively charged ridge is present on the opposite face of the protein. These surfaces may be important sites of interaction with other proteins involved in the replication process. Together, the structure and NMR assignments should facilitate the design of new experiments to probe the protein-protein interactions essential for the initiation of DNA replication.

  7. Tor forms a dimer through an N-terminal helical solenoid with a complex topology

    Science.gov (United States)

    Baretić, Domagoj; Berndt, Alex; Ohashi, Yohei; Johnson, Christopher M.; Williams, Roger L.

    2016-04-01

    The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a range of anabolic and catabolic processes. Tor is present in two complexes, TORC1 and TORC2, in which the Tor-Lst8 heterodimer forms a common sub-complex. We have determined the cryo-electron microscopy (EM) structure of Tor bound to Lst8. Two Tor-Lst8 heterodimers assemble further into a dyad-symmetry dimer mediated by Tor-Tor interactions. The first 1,300 residues of Tor form a HEAT repeat-containing α-solenoid with four distinct segments: a highly curved 800-residue N-terminal 'spiral', followed by a 400-residue low-curvature 'bridge' and an extended `railing' running along the bridge leading to the 'cap' that links to FAT region. This complex topology was verified by domain insertions and offers a new interpretation of the mTORC1 structure. The spiral of one TOR interacts with the bridge of another, which together form a joint platform for the Regulatory Associated Protein of TOR (RAPTOR) regulatory subunit.

  8. PrP N-terminal domain triggers PrP(Sc)-like aggregation of Dpl.

    Science.gov (United States)

    Erlich, Paul; Cesbron, Jean-Yves; Lemaire-Vieille, Catherine; Curt, Aurélie; Andrieu, Jean-Pierre; Schoehn, Guy; Jamin, Marc; Gagnon, Jean

    2008-01-18

    Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP(C), for "cellular prion protein") into an abnormal state (PrP(Sc), for "scrapie prion protein"). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP(C). In contrast to its homologue PrP(C), Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP(Sc)-like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP(C) (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the alpha-helical monomer forms soluble beta-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy.

  9. Structure of the N-terminal region of Haemophilus Influenzae HI0017: Implications for function

    Energy Technology Data Exchange (ETDEWEB)

    Yu Liping; Mack, Jamey; Hajduk, Phil; Fesik, Stephen W. [Abbott Laboratories, Pharmaceutical Discovery Division, D46Y, AP10/LL (United States)

    2001-06-15

    Haemophilus influenzae is a gram-negative pathogen that causes infections ranging from asymptomatic colonization of the human upper respiratory tract to serious invasive diseases such as meningitis. Although the genome of Haemophilus influenzae has been completely sequenced, the structure and function of many of these proteins are unknown. HI0017 is one of these uncharacterized proteins. Here we describe the three-dimensional solution structure of the N-terminal portion of HI0017 as determined by NMR spectroscopy. The structure consists of a five-stranded antiparallel {beta}-sheet and two short {alpha}-helices. It is similar to the C-terminal domain of Diphtheria toxin repressor (DtxR). The C-terminal portion of HI0017 has an amino acid sequence that closely resembles pyruvate formate-lyase - an enzyme that converts pyruvate and CoA into acetyl-CoA and formate by a radical mechanism. Based on structural and sequence comparisons, we propose that the C-terminus of HI0017 functions as an enzyme with a glycyl radical mechanism, while the N-terminus participates in protein/protein interactions involving an activase (iron-sulfur protein) and/or the substrate.

  10. Structure of the N-terminal region of Haemophilus Influenzae HI0017: Implications for function

    International Nuclear Information System (INIS)

    Yu Liping; Mack, Jamey; Hajduk, Phil; Fesik, Stephen W.

    2001-01-01

    Haemophilus influenzae is a gram-negative pathogen that causes infections ranging from asymptomatic colonization of the human upper respiratory tract to serious invasive diseases such as meningitis. Although the genome of Haemophilus influenzae has been completely sequenced, the structure and function of many of these proteins are unknown. HI0017 is one of these uncharacterized proteins. Here we describe the three-dimensional solution structure of the N-terminal portion of HI0017 as determined by NMR spectroscopy. The structure consists of a five-stranded antiparallel β-sheet and two short α-helices. It is similar to the C-terminal domain of Diphtheria toxin repressor (DtxR). The C-terminal portion of HI0017 has an amino acid sequence that closely resembles pyruvate formate-lyase - an enzyme that converts pyruvate and CoA into acetyl-CoA and formate by a radical mechanism. Based on structural and sequence comparisons, we propose that the C-terminus of HI0017 functions as an enzyme with a glycyl radical mechanism, while the N-terminus participates in protein/protein interactions involving an activase (iron-sulfur protein) and/or the substrate

  11. Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences.

    LENUS (Irish Health Repository)

    Ivanov, Ivaylo P

    2011-05-01

    In eukaryotes, it is generally assumed that translation initiation occurs at the AUG codon closest to the messenger RNA 5\\' cap. However, in certain cases, initiation can occur at codons differing from AUG by a single nucleotide, especially the codons CUG, UUG, GUG, ACG, AUA and AUU. While non-AUG initiation has been experimentally verified for a handful of human genes, the full extent to which this phenomenon is utilized--both for increased coding capacity and potentially also for novel regulatory mechanisms--remains unclear. To address this issue, and hence to improve the quality of existing coding sequence annotations, we developed a methodology based on phylogenetic analysis of predicted 5\\' untranslated regions from orthologous genes. We use evolutionary signatures of protein-coding sequences as an indicator of translation initiation upstream of annotated coding sequences. Our search identified novel conserved potential non-AUG-initiated N-terminal extensions in 42 human genes including VANGL2, FGFR1, KCNN4, TRPV6, HDGF, CITED2, EIF4G3 and NTF3, and also affirmed the conservation of known non-AUG-initiated extensions in 17 other genes. In several instances, we have been able to obtain independent experimental evidence of the expression of non-AUG-initiated products from the previously published literature and ribosome profiling data.

  12. Mcm10 self-association is mediated by an N-terminal coiled-coil domain.

    Directory of Open Access Journals (Sweden)

    Wenyue Du

    Full Text Available Minichromosome maintenance protein 10 (Mcm10 is an essential eukaryotic DNA-binding replication factor thought to serve as a scaffold to coordinate enzymatic activities within the replisome. Mcm10 appears to function as an oligomer rather than in its monomeric form (or rather than as a monomer. However, various orthologs have been found to contain 1, 2, 3, 4, or 6 subunits and thus, this issue has remained controversial. Here, we show that self-association of Xenopus laevis Mcm10 is mediated by a conserved coiled-coil (CC motif within the N-terminal domain (NTD. Crystallographic analysis of the CC at 2.4 Å resolution revealed a three-helix bundle, consistent with the formation of both dimeric and trimeric Mcm10 CCs in solution. Mutation of the side chains at the subunit interface disrupted in vitro dimerization of both the CC and the NTD as monitored by analytical ultracentrifugation. In addition, the same mutations also impeded self-interaction of the full-length protein in vivo, as measured by yeast-two hybrid assays. We conclude that Mcm10 likely forms dimers or trimers to promote its diverse functions during DNA replication.

  13. Autocatalytic activity and substrate specificity of the pestivirus N-terminal protease Npro

    International Nuclear Information System (INIS)

    Gottipati, Keerthi; Acholi, Sudheer; Ruggli, Nicolas; Choi, Kyung H.

    2014-01-01

    Pestivirus N pro is the first protein translated in the viral polypeptide, and cleaves itself off co-translationally generating the N-terminus of the core protein. Once released, N pro blocks the host's interferon response by inducing degradation of interferon regulatory factor-3. N pro' s intracellular autocatalytic activity and lack of trans-activity have hampered in vitro cleavage studies to establish its substrate specificity and the roles of individual residues. We constructed N pro -GFP fusion proteins that carry the authentic cleavage site and determined the autoproteolytic activities of N pro proteins containing substitutions at the predicted catalytic sites Glu22 and Cys69, at Arg100 that forms a salt bridge with Glu22, and at the cleavage site Cys168. Contrary to previous reports, we show that N pro' s catalytic activity does not involve Glu22, which may instead be involved in protein stability. Furthermore, N pro does not have specificity for Cys168 at the cleavage site even though this residue is conserved throughout the pestivirus genus. - Highlights: • N pro' s autoproteolysis is studied using N pro -GFP fusion proteins. • N-terminal 17 amino acids are dispensable without loss of protease activity. • The putative catalytic residue Glu22 is not involved in protease catalysis. • No specificity for Cys168 at the cleavage site despite evolutionary conservation. • N pro prefers small amino acids with non-branched beta carbons at the P1 position

  14. Prospective evaluation of risk factors for exercise-induced hypogonadism in male runners.

    Science.gov (United States)

    Skarda, S T; Burge, M R

    1998-01-01

    Exercise-induced hypogonadotropic hypogonadism is well recognized among female endurance athletes but is less commonly observed in male endurance athletes. We have reported a well-characterized case of severe acquired hypogonadotropic hypogonadism in a male distance runner with osteopenia, stress fracture, and sexual dysfunction. Using this case as an index, we hypothesized that the presence of 1 or more specific risk factors would prospectively identify male endurance athletes with exercise-induced hypogonadotropic hypogonadism. These include a history of stress fracture, sexual dysfunction, or the initiation of endurance exercise before age 18 years. We studied 28 male endurance runners younger than 50 years who ran more than 40 miles per week. Of these runners, 15 had 1 or more of the above risk factors (group 1), and the remaining 13 had none of the putative risk factors (group 2). A group of 10 sedentary control subjects was also studied (group 3). There was no difference between groups 1 and 2 in weekly training mileage. Group 1 was younger than group 2 (32 +/- 10 years versus 39 +/- 6 years, P bioelectric impedance, preliminary data showed that group 1 had a reduced body fat content (group 1, 14.5% +/- 2.8%; group 2, 16.9% +/- 2.0%; and group 3, 17.5% +/- 4.1%; P .05). One subject with primary hypogonadism was identified in group 1. The presence of the aforementioned risk factors does not predict the occurrence of exercise-induced hypogonadotropic hypogonadism among male endurance runners in this pilot study. A larger sample size or more discriminating risk factors (or both) may be necessary to identify this uncommon but potentially debilitating condition. PMID:9682624

  15. Natriuretic peptides (BNP and NT-proBNP: measurement and relevance in heart failure

    Directory of Open Access Journals (Sweden)

    A Palazzuoli

    2010-05-01

    Full Text Available A Palazzuoli, M Gallotta, I Quatrini, R NutiDepartment of Internal Medicine and Metabolic Diseases, Section of Cardiology “Le Scotte” Hospital, University of Siena, ItalyAbstract: For patients presenting with acute dyspnea, an incorrect diagnosis could increase the mortality risk. When used in the evaluation of patients with acute symptoms, brain natriuretic peptide and N-terminal pro-brain natriuretic peptide (BNP and NT-proBNP, respectively testing is highly sensitive for the diagnosis or exclusion of acute or chronic decompensated heart failure (HF. It has been demonstrated that BNP and proBNP levels can facilitate diagnosis and guide HF therapy. Natriuretic peptide (NP levels are strictly related with HF severity; they are particularly increased in more advanced New York Heart Association (NYHA classes and in patients with poor outcome. Therefore elevated NP levels were found to correlate with the severity of left ventricular systolic dysfunction, right ventricular dysfunction and pressures, and left ventricular filling alterations. However, the optimal use of NP determination agrees with patient history, physical examination, and all other diagnostic tools. There are some clinical conditions (ie, obesity, renal insufficiency anemia for which the NP measurement is not diagnostic. Algorithm building taking into consideration all clinical and echocardiographic parameters, as well as NP measurements, may lead to the earlier identification and better risk stratification of patients with chronic HF, independently from etiology.Keywords: heart failure, diagnosis, echocardiography, natriuretic pepides

  16. Relationship between exercise-induced bronchospasm (EIB) and asthma control test (ACT) in asthmatic children.

    Science.gov (United States)

    Rapino, Daniele; Consilvio, Nicola Pietro; Pietroconsilvio, Nicola; Scaparrotta, Alessandra; Cingolani, Anna; Attanasi, Marina; Di Pillo, Sabrina; Pillo, Sabrina Di; Verini, Marcello; Chiarelli, Francesco

    2011-12-01

    Evaluate the relationship between Asthma Control Test™ (ACT) and exercise-induced bronchospasm (EIB) in 81 asthmatic children. EIB was assessed in every patient by Balke protocol and asthma control was evaluated by ACT. Patients were divided into three groups: Group A (30 patients) with complete asthma control (ACT score = 25), Group B (37 patients) with partial asthma control (ACT score = 21-24), and Group C (14 patients) with poor asthma control (ACT score children correctly because it fails to detect EIB in a significant percentage of subjects.

  17. Polyphenols: well beyond the antioxidant capacity: polyphenol supplementation and exercise-induced oxidative stress and inflammation.

    Science.gov (United States)

    Sureda, Antoni; Tejada, Silvia; Bibiloni, Maria del Mar; Tur, Josep Antoni; Pons, Antoni

    2014-01-01

    Moderate physical exercise leads the organism to adapt to this stressful situation. However, when exercise is exhaustive, it is also known to induce an overproduction of reactive species which can result in oxidative damage to macromolecules and tissues. Many studies have been carried out to evaluate the validity of dietary strategies or micronutrients in order to attenuate exercise-induced oxidative stress. Polyphenols are a large group of compounds widely distributed throughout the plant kingdom. This review summarizes recent evidence in relation to the effects of polyphenols as antioxidant and anti-inflammatory agents, using exercise as a model of study.

  18. Exercise-induced acute compartment syndrome in a young man, occurring after a short race

    OpenAIRE

    Basnet, Bibhusan; Matar, Mousa; Vaitilingham, Siddharthan; Chalise, Shyam; Irooegbu, Nkem; Bang, Jane

    2016-01-01

    We describe a case of exercise-induced acute compartment syndrome (ACS) in a 23-year-old man who presented to his primary care physician 48 hours after he attempted to run a 5K race. He noticed searing pain in his left leg after the first half mile but had no other symptoms. He was referred to the emergency department and diagnosed with ACS, and a fasciotomy was done. A presentation of limb pain that is out of proportion to a known or suspected injury should prompt consideration of ACS. Early...

  19. Exercise-induced acute compartment syndrome in a young man, occurring after a short race.

    Science.gov (United States)

    Basnet, Bibhusan; Matar, Mousa; Vaitilingham, Siddharthan; Chalise, Shyam; Irooegbu, Nkem; Bang, Jane

    2016-04-01

    We describe a case of exercise-induced acute compartment syndrome (ACS) in a 23-year-old man who presented to his primary care physician 48 hours after he attempted to run a 5K race. He noticed searing pain in his left leg after the first half mile but had no other symptoms. He was referred to the emergency department and diagnosed with ACS, and a fasciotomy was done. A presentation of limb pain that is out of proportion to a known or suspected injury should prompt consideration of ACS. Early recognition and surgical management are essential to achieving the best possible outcome.

  20. An update on exercise-induced bronchoconstriction with and without asthma.

    Science.gov (United States)

    Randolph, Chris

    2009-11-01

    Exercise-induced bronchoconstriction (EIB) is defined as transient, reversible bronchoconstriction that develops after strenuous exercise. It is a heterogeneous syndrome made up of a spectrum of phenotypes ranging from the asymptomatic military recruit whose condition is detected by diagnostic exercise challenge to the athlete with known asthma to the elite athlete for whom EIB represents an overuse or injury syndrome. If exercise is the only identified trigger for bronchoconstriction, it is called EIB. However, when it is associated with known asthma, then it is defined as EIB with asthma. This review discusses the pathogenesis, presentation, diagnosis, and management of EIB and EIB with asthma.

  1. Exercise-induced Atrioventricular Block with Coronary Artery Stenosis that Appeared Five Years after Bypass Surgery.

    Science.gov (United States)

    Yamazaki, Shinya; Kato, Taku; Ushimaru, Shunpei; Yokoi, Hirokazu; Mani, Hiroki

    2018-02-01

    A 68-year-old man with a history of coronary artery bypass surgery was referred to our hospital because of pre-syncope on effort. During a treadmill exercise electrocardiogram test, the patient developed advanced atrioventricular block associated with dizziness. Coronary angiography revealed significant stenosis of the right coronary artery, which had not existed at the time of the bypass surgery. We implanted drug-eluting stents in the stenotic lesion, and an exercise test showed resolution of the atrioventricular block. Exercise-induced atrioventricular block is rare, and it is necessary to distinguish it from ischemic heart disease, especially in patients with a history of coronary artery disease.

  2. Distinct Molecular Regulation of Glycogen Synthase Kinase-3α Isozyme Controlled by Its N-terminal Region

    Science.gov (United States)

    Azoulay-Alfaguter, Inbar; Yaffe, Yakey; Licht-Murava, Avital; Urbanska, Malgorzata; Jaworski, Jacek; Pietrokovski, Shmuel; Hirschberg, Koret; Eldar-Finkelman, Hagit

    2011-01-01

    Glycogen synthase kinase-3 (GSK-3) is expressed as two isozymes α and β. They share high similarity in their catalytic domains but differ in their N- and C-terminal regions, with GSK-3α having an extended glycine-rich N terminus. Here, we undertook live cell imaging combined with molecular and bioinformatic studies to understand the distinct functions of the GSK-3 isozymes focusing on GSK-3α N-terminal region. We found that unlike GSK-3β, which shuttles between the nucleus and cytoplasm, GSK-3α was excluded from the nucleus. Deletion of the N-terminal region of GSK-3α resulted in nuclear localization, and treatment with leptomycin B resulted in GSK-3α accumulation in the nucleus. GSK-3α rapidly accumulated in the nucleus in response to calcium or serum deprivation, and accumulation was strongly inhibited by the calpain inhibitor calpeptin. This nuclear accumulation was not mediated by cleavage of the N-terminal region or phosphorylation of GSK-3α. Rather, we show that calcium-induced GSK-3α nuclear accumulation was governed by GSK-3α binding with as yet unknown calpain-sensitive protein or proteins; this binding was mediated by the N-terminal region. Bioinformatic and experimental analyses indicated that nuclear exclusion of GSK-3α was likely an exclusive characteristic of mammalian GSK-3α. Finally, we show that nuclear localization of GSK-3α reduced the nuclear pool of β-catenin and its target cyclin D1. Taken together, these data suggest that the N-terminal region of GSK-3α is responsible for its nuclear exclusion and that binding with a calcium/calpain-sensitive product enables GSK-3α nuclear retention. We further uncovered a novel link between calcium and nuclear GSK-3α-mediated inhibition of the canonical Wnt/β-catenin pathway. PMID:21266584

  3. N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Boesen, Mikael; Olsen, Michael

    2004-01-01

    In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value...... is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT-proBNP was eight-fold higher than in healthy subjects. The log NT-proBNP correlated with LV mass index (R=0...

  4. Strength and fatigue of NT551 silicon nitride and NT551 diesel exhaust valves

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, M.J.; Werezczak, A.A.; Kirkland, T.P.; Breder, K.

    2000-02-01

    The content of this report is excerpted from Mark Andrew's Ph.D. Thesis (Andrews, 1999), which was funded by a DOE/OTT High Temperature Materials Laboratory Graduate Fellowship. It involves the characterization of NT551 and valves fabricated with it. The motivations behind using silicon nitride (Si{sub 3}N{sub 4}) as an exhaust valve for a diesel engine are presented in this section. There are several economic factors that have encouraged the design and implementation of ceramic components for internal combustion (IC) engines. The reasons for selecting the diesel engine valve for this are also presented.

  5. Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s.

    Science.gov (United States)

    Gu, Qinyong; Zhang, Zeli; Cano Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter; Münk, Carsten

    2016-12-01

    Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain. Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z

  6. Subjective and objective assessment of physical activity - Influence of newly diagnosed exercise induced bronchoconstriction and gender.

    Science.gov (United States)

    Johansson, Henrik; Berglund, Marie; Holmbäck, Ulf

    2017-10-01

    To investigate if occurrence of newly diagnosed exercise induced bronchoconstriction (EIB) would affect adolescents' ability to assess their physical activity. 99 selected adolescents with and 47 adolescents without self-reported exercise induced dyspnea were included. All of the 146 adolescents then performed a standardized exercise challenge test on a treadmill with dry-air inhalation to detect EIB. Free living physical activity was assessed during seven days with both accelerometer (objective assessment) and a validated activity diary (subjective assessment). Height, weight and subjective sleep were recorded. Out of the 146 adolescents 49 were diagnosed with EIB. Forty-six of the adolescents with EIB (35 girls and 11 boys) and 84 of the control adolescents (45 girls and 39 boys) had complete 7 day activity diary and accelerometer data. There were no differences in age, BMI and sleep between EIB and control adolescents. Boys with EIB overestimated subjective assessment compared to objective assessment more than girls with EIB. No difference was seen between control boys and girls. Furthermore, boys with EIB reported a much higher frequency of high intensity exercise than girls with EIB, but no difference was observed between control boys and girls. Adolescent boys with newly diagnosed EIB overestimated their physical activity compared to EIB girls. Caution may thus be used when choosing methods measuring level of physical activity in this group and especially when investigating gender differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Exercise-induced ventricular arrhythmias: analysis of predictive factors in a population with sleep disorders

    Directory of Open Access Journals (Sweden)

    Fatima Dumas Cintra

    2010-03-01

    Full Text Available Objective: To assess the prevalence of ventricular arrhythmias induced by exercise in a population with sleep disorders and to analyze the triggering factors. Methods: Patients were consecutively selected from the database of the Sleep Clinic of Universidade Federal de São Paulo. All subjects were submitted to basal polysomnography, blood sample collection, physical examination, 12-lead ECG, spirometry, cardiorespiratory exercise study on a treadmill, and echocardiogram. The Control Group was matched for age and gender. Results: A total of 312 patients were analyzed. Exercise-induced ventricular arrhythmia was observed in 7%. The aortic diameter was larger (3.44 ± 0.30, 3.16 ± 0.36, p = 0.04 and the minimal saturation was lower (92.75 ± 3.05, 95.50 ± 1.73, p=0.01 in the ventricular arrhythmia group when compared to controls, respectively. After correction of the aortic root to body surface, there was only a trend to a larger diameter being associated with the emergence of arrhythmia. Conclusions: Exercise-induced ventricular arrhythmia was observed in 7% of sample and it was associated with lower oxygen saturation during exercise.

  8. Exercise-induced changes in EEG alpha power depend on frequency band definition mode.

    Science.gov (United States)

    Gutmann, Boris; Hülsdünker, Thorben; Mierau, Julia; Strüder, Heiko K; Mierau, Andreas

    2018-01-01

    In the majority of studies investigating cortical alpha oscillations the alpha frequency is defined as a fixed band thus, neglecting recommendations in the EEG literature to adjust the alpha band according to the individual alpha peak frequency (iAPF). Based on our previous findings indicating exhaustive exercise induces an increase of the post-exercise iAPF, we scrutinized the influence of exercise on post-exercise alpha power by comparing fixed and iAPF-adjusted alpha frequency bands. Resting EEG was recorded from 13 scalp locations in nine subjects before, immediately after as well as ten minutes following an exhaustive exercise protocol on a cycle ergometer. Lower and upper band alpha power was calculated for fixed and iAPF-adjusted frequency bands. Post-exercise lower alpha power increased in both fixed and individually defined bands while a higher upper alpha power was only observed in the fixed frequency band condition. Further, the increase in iAPF was positively related to the changes in fixed-band upper alpha power. It is concluded that lower alpha power is significantly increased following exhaustive exercise whereas the results for upper alpha power are substantially influenced by the method of frequency band definition. Therefore, caution is indicated when analyzing and interpreting exercise-induced changes in alpha power. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Exercise-induced bronchospasm: implications for patients with or without asthma in primary care practice

    Directory of Open Access Journals (Sweden)

    Hayden ML

    2011-11-01

    Full Text Available Stuart W Stoloff1, Gene L Colice2, Mary Lou Hayden3, Timothy J Craig4, Nancy K Ostrom5, Nemr S Eid6, Jonathan P Parsons71University of Nevada School of Medicine, Reno, NV, 2Washington Hospital Center, Washington, DC, 3University of Virginia, Charlottesville, VA, 4Pennsylvania State University, Hershey, PA, 5Allergy and Asthma Medical Group and Research Center, San Diego, CA, 6University of Louisville, Louisville, KY, 7Ohio State University Asthma Center, Columbus, OH, USAAbstract: Exercise-induced bronchospasm (EIB can represent a substantial barrier to physical activity. We present the cases of two patients with EIB, one with asthma, and one without asthma, who were evaluated at our primary care practice. The first case was a 44-year-old man with a history of seasonal allergic rhinitis but no asthma, who reported difficulty breathing when playing tennis. The second case was a 45-year-old woman who presented with persistent, generally well-controlled asthma, who was now experiencing bouts of coughing and wheezing during exercise. In both cases, an exercise challenge was used to diagnose EIB, and patients were prescribed a short-acting beta agonist to be used immediately before initiating exercise. EIB is a frequently encountered problem among patients presenting to primary care specialists. Affected patients should be made aware of the importance of proactive treatment with a short-acting beta agonist before initiating any exercise.Keywords: asthma, compliance, exercise-induced bronchospasm

  10. Adaptations to endurance training depend on exercise-induced oxidative stress: exploiting redox interindividual variability.

    Science.gov (United States)

    Margaritelis, N V; Theodorou, A A; Paschalis, V; Veskoukis, A S; Dipla, K; Zafeiridis, A; Panayiotou, G; Vrabas, I S; Kyparos, A; Nikolaidis, M G

    2018-02-01

    The aim of this study was to reveal the role of reactive oxygen and nitrogen species (RONS) in exercise adaptations under physiological in vivo conditions and without the interference from other exogenous redox agents (e.g. a pro-oxidant or antioxidant). We invented a novel methodological set-up that exploited the large redox interindividual variability in exercise responses. More specifically, we used exercise-induced oxidative stress as the 'classifier' measure (i.e. low, moderate and high) and investigated the physiological and redox adaptations after a 6-week endurance training protocol. We demonstrated that the group with the low exercise-induced oxidative stress exhibited the lowest improvements in a battery of classic adaptations to endurance training (VO 2 max, time trial and Wingate test) as well as in a set of redox biomarkers (oxidative stress biomarkers and antioxidants), compared to the high and moderate oxidative stress groups. The findings of this study substantiate, for the first time in a human in vivo physiological context, and in the absence of any exogenous redox manipulation, the vital role of RONS produced during exercise in adaptations. The stratification approach, based on a redox phenotype, implemented in this study could be a useful experimental strategy to reveal the role of RONS and antioxidants in other biological manifestations as well. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  11. Exercise-induced interstitial pulmonary edema at sea-level in young and old healthy humans.

    Science.gov (United States)

    Taylor, Bryan J; Carlson, Alex R; Miller, Andrew D; Johnson, Bruce D

    2014-01-15

    We asked whether aged adults are more susceptible to exercise-induced pulmonary edema relative to younger individuals. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (Dm) and pulmonary-capillary blood volume (Vc) were measured before and after exhaustive discontinuous incremental exercise in 10 young (YNG; 27±3 years) and 10 old (OLD; 69±5 years) males. In YNG subjects, Dm increased (11±7%, P=0.031), Vc decreased (-10±9%, P=0.01) and DLCO was unchanged (30.5±4.1 vs. 29.7±2.9mL/min/mmHg, P=0.44) pre- to post-exercise. In OLD subjects, DLCO and Dm increased (11±14%, P=0.042; 16±14%, P=0.025) but Vc was unchanged (58±23 vs. 56±23mL, P=0.570) pre- to post-exercise. Group-mean Dm/Vc was greater after vs. before exercise in the YNG and OLD subjects. However, Dm/Vc was lower post-exercise in 2 of the 10 YNG (-7±4%) and 2 of the 10 OLD subjects (-10±5%). These data suggest that exercise decreases interstitial lung fluid in most YNG and OLD subjects, with a small number exhibiting evidence for exercise-induced pulmonary edema. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.

    Science.gov (United States)

    Galdino, Giovane; Romero, Thiago R L; Silva, José Felipe P; Aguiar, Daniele C; de Paula, Ana Maria; Cruz, Jader S; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor D; Di Marzo, Vincenzo; Perez, Andrea C

    2014-02-01

    Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB₁ and CB₂ cannabinoid receptor antagonists (AM251 and AM630) blocked the antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Western blot analysis revealed an increase and activation of CB₁ receptors in the rat brain, and immunofluorescence analysis demonstrated an increase of activation and expression of CB₁ receptors in neurons of the periaqueductal gray matter (PAG) after exercise. Additionally, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise could activate the endocannabinoid system, producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE. Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Use of Saliva Biomarkers to Monitor Efficacy of Vitamin C in Exercise-Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Levi W. Evans

    2017-01-01

    Full Text Available Saliva is easily obtainable for medical research and requires little effort or training for collection. Because saliva contains a variety of biological compounds, including vitamin C, malondialdehyde, amylase, and proteomes, it has been successfully used as a biospecimen for the reflection of health status. A popular topic of discussion in medical research is the potential association between oxidative stress and negative outcomes. Systemic biomarkers that represent oxidative stress can be found in saliva. It is unclear, however, if saliva is an accurate biospecimen as is blood and/or plasma. Exercise can induce oxidative stress, resulting in a trend of antioxidant supplementation to combat its assumed detriments. Vitamin C is a popular antioxidant supplement in the realm of sports and exercise. One potential avenue for evaluating exercise induced oxidative stress is through assessment of biomarkers like vitamin C and malondialdehyde in saliva. At present, limited research has been done in this area. The current state of research involving exercise-induced oxidative stress, salivary biomarkers, and vitamin C supplementation is reviewed in this article.

  14. Acute relief of exercise-induced bronchoconstriction by inhaled formoterol in children with persistent asthma

    DEFF Research Database (Denmark)

    Hermansen, Mette Northman; Nielsen, Kim Gjerum; Buchvald, Frederik

    2006-01-01

    STUDY OBJECTIVE: To compare the acute bronchodilatory effect of the long-acting beta2-agonist formoterol against the short-acting beta2-agonist (SABA) terbutaline during exercise-induced bronchoconstriction (EIB) in children with asthma. DESIGN: A randomized, double-blind, placebo-controlled, cro......STUDY OBJECTIVE: To compare the acute bronchodilatory effect of the long-acting beta2-agonist formoterol against the short-acting beta2-agonist (SABA) terbutaline during exercise-induced bronchoconstriction (EIB) in children with asthma. DESIGN: A randomized, double-blind, placebo......-controlled, crossover study of the immediate effect of formoterol, 9 microg, vs terbutaline, 0.5 mg, and placebo administered as dry powder at different study days. Exercise challenge test was used as a model of acute bronchoconstriction. PATIENTS: Twenty-four 7- to 15-year-old children with persistent asthma...... in schoolchildren with persistent asthma. Formoterol is at least as effective as SABA and may be considered an alternative in the treatment of acute bronchoconstriction in school children....

  15. Exercise-induced interstitial pulmonary edema at sea-level in young and old healthy humans

    Science.gov (United States)

    Taylor, Bryan J.; Carlson, Alex R.; Miller, Andrew D.; Johnson, Bruce D.

    2014-01-01

    We asked whether aged adults are more susceptible to exercise-induced pulmonary edema relative to younger individuals. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (Dm) and pulmonary-capillary blood volume (Vc) were measured before and after exhaustive discontinuous incremental exercise in 10 young (YNG; 27±3 yr) and 10 old (OLD; 69±5 yr) males. In YNG subjects, Dm increased (11±7%, P=0.031), Vc decreased (−10±9%, P=0.01) and DLCO was unchanged (30.5±4.1 vs. 29.7±2.9 ml/min/mmHg, P=0.44) pre- to post-exercise. In OLD subjects, DLCO and Dm increased (11±14%, P=0.042; 16±14%, P=0.025) but Vc was unchanged (58±23 vs. 56±23 ml, P=0.570) pre- to post-exercise. Group-mean Dm/Vc was greater after vs. before exercise in the YNG and OLD subjects. However, Dm/Vc was lower post-exercise in 2 of the 10 YNG (−7±4%) and 2 of the 10 OLD subjects (−10±5%). These data suggest that exercise decreases interstitial lung fluid in most YNG and OLD subjects, with a small number exhibiting evidence for exercise-induced pulmonary edema. PMID:24200644

  16. Exercise-induced muscle glucose uptake in mice with graded, muscle-specific GLUT-4 deletion

    Science.gov (United States)

    Howlett, Kirsten F; Andrikopoulos, Sofianos; Proietto, Joseph; Hargreaves, Mark

    2013-01-01

    To investigate the importance of the glucose transporter GLUT-4 for muscle glucose uptake during exercise, transgenic mice with skeletal muscle GLUT-4 expression approximately 30–60% of normal (CON) and approximately 5–10% of normal (KO) were generated using the Cre/Lox system and compared with wild-type (WT) mice during approximately 40 min of treadmill running (KO: 37.7 ± 1.3 min; WT: 40 min; CON: 40 min, P = 0.18). In WT and CON animals, exercise resulted in an overall increase in muscle glucose uptake. More specifically, glucose uptake was increased in red gastrocnemius of WT mice and in the soleus and red gastrocnemius of CON mice. In contrast, the exercise-induced increase in muscle glucose uptake in all muscles was completely abolished in KO mice. Muscle glucose uptake increased during exercise in both red and white quadriceps of WT mice, while the small increases in CON mice were not statistically significant. In KO mice, there was no change at all in quadriceps muscle glucose uptake. No differences in muscle glycogen use during exercise were observed between any of the groups. However, there was a significant increase in plasma glucose levels after exercise in KO mice. The results of this study demonstrated that a reduction in skeletal muscle GLUT-4 expression to approximately 10% of normal levels completely abolished the exercise-induced increase in muscle glucose uptake. PMID:24303141

  17. Benefits of dietary phytochemical supplementation on eccentric exercise-induced muscle damage: Is including antioxidants enough?

    Science.gov (United States)

    Pereira Panza, Vilma Simões; Diefenthaeler, Fernando; da Silva, Edson Luiz

    2015-09-01

    The purpose of this review was to critically discuss studies that investigated the effects of supplementation with dietary antioxidant phytochemicals on recovery from eccentric exercise-induced muscle damage. The performance of physical activities that involve unaccustomed eccentric muscle actions-such as lowering a weight or downhill walking-can result in muscle damage, oxidative stress, and inflammation. These events may be accompanied by muscle weakness and delayed-onset muscle soreness. According to the current evidences, supplementation with dietary antioxidant phytochemicals appears to have the potential to attenuate symptoms associated with eccentric exercise-induced muscle damage. However, there are inconsistencies regarding the relationship between muscle damage and blood markers of oxidative stress and inflammation. Furthermore, the effectiveness of strategies appear to depend on a number of aspects inherent to phytochemical compounds as well as its food matrix. Methodological issues also may interfere with the proper interpretation of supplementation effects. Thus, the study may contribute to updating professionals involved in sport nutrition as well as highlighting the interest of scientists in new perspectives that can widen dietary strategies applied to training. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The Role of Episodic Postprandial Peptides in Exercise-Induced Compensatory Eating.

    Science.gov (United States)

    Gibbons, Catherine; Blundell, John E; Caudwell, Phillipa; Webb, Dominic-Luc; Hellström, Per M; Näslund, Erik; Finlayson, Graham

    2017-11-01

    Prolonged physical activity gives rise to variable degrees of body weight and fat loss, and is associated with variability in appetite control. Whether these effects are modulated by postprandial, peptides is unclear. We examined the role of postprandial peptide response in compensatory eating during 12 weeks of aerobic exercise and in response to high-fat, low-carbohydrate (HFLC) and low-fat, high-carbohydrate (LFHC) meals. Of the 32 overweight/obese individuals, 16 completed 12 weeks of aerobic exercise and 16 nonexercising control subjects were matched for age and body mass index. Exercisers were classified as responders or nonresponders depending on net energy balance from observed compared with expected body composition changes from measured energy expenditure. Plasma samples were collected before and after meals to compare profiles of total and acylated ghrelin, insulin, cholecystokinin, glucagon-like peptide 1 (GLP-1), and total peptide YY (PYY) between HFLC and LFHC meals, pre- and postexercise, and between groups. No differences between pre- and postintervention peptide release. Responders had greater suppression of acylated ghrelin (P exercise. Responders to exercise-induced weight loss showed greater suppression of acylated ghrelin and greater release of GLP-1 and total PYY at baseline. Therefore, episodic postprandial peptide profiles appear to form part of the pre-existing physiology of exercise responders and suggest differences in satiety potential may underlie exercise-induced compensatory eating. Copyright © 2017 Endocrine Society

  19. Exercise-induced silent myocardial ischemia: Evaluation by thallium-201 emission computed tomography

    International Nuclear Information System (INIS)

    Kurata, C.; Sakata, K.; Taguchi, T.; Kobayashi, A.; Yamazaki, N.

    1990-01-01

    Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and 57 (50%) of 115 with ischemia and angiographically documented CAD had no chest pain. One third of the patients showed an inconsistency between scintigraphic ischemia and ischemia ST depression. Age, sex, prior myocardial infarction, and diabetes mellitus were not related to SMI. Patients with SMI had less severe ischemia despite a higher peak double product compared to those with painful ischemia. Among 91 with prior myocardial infarction and exercise-induced ischemia, 51 with periinfarction ischemia had a higher frequency of SMI than did 14 with ischemia remote from the prior infarct zone despite similarities in the severity of ischemia. In conclusion, factors localized within ischemic myocardium such as less severe ischemia or adjacency to a prior infarct made SMI more prevalent

  20. Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia

    Directory of Open Access Journals (Sweden)

    G. Camus

    1998-01-01

    Full Text Available To address the question of whether translocation of bacterial lipopolysaccharide (LPS into the blood could be involved in the process of exercise-induced polymorphonuclear neutrophil (PMN activation, 12 healthy male subjects who took part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road race were studied. While there was no detectable amount of endotoxin in the blood samples drawn at rest, exercise was followed by the appearance of circulating endotoxin molecules at the end of competition in four subjects, and after one and 24 h recovery in three and seven athletes, respectively. The concentrations of plasma granulocyte myeloperoxidase ([MPO], were significantly higher immediately after exercise and one hour later than baseline values (P<0.001. This variable returned to pre-race levels the day after exercise, despite the presence of detectable amounts of LPS, at that time, in seven athletes. The absence of significant correlation (r=0.26;P=0.383 and temporal association between [MPO]and plasma endotoxin levels led us to conclude that endotoxaemia was not involved in the process of exercise-induced PMN degranulation observed in our subjects.

  1. Simulation of Exercise-Induced Syncope in a Heart Model with Severe Aortic Valve Stenosis

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    Matjaž Sever

    2012-01-01

    Full Text Available Severe aortic valve stenosis (AVS can cause an exercise-induced reflex syncope (RS. The precise mechanism of this syncope is not known. The changes in hemodynamics are variable, including arrhythmias and myocardial ischemia, and one of the few consistent changes is a sudden fall in systemic and pulmonary arterial pressures (suggesting a reduced vascular resistance followed by a decline in heart rate. The contribution of the cardioinhibitory and vasodepressor components of the RS to hemodynamics was evaluated by a computer model. This lumped-parameter computer simulation was based on equivalent electronic circuits (EECs that reflect the hemodynamic conditions of a heart with severe AVS and a concomitantly decreased contractility as a long-term detrimental consequence of compensatory left ventricular hypertrophy. In addition, the EECs model simulated the resetting of the sympathetic nervous tone in the heart and systemic circuit during exercise and exercise-induced syncope, the fluctuating intra-thoracic pressure during respiration, and the passive relaxation of ventricle during diastole. The results of this simulation were consistent with the published case reports of exertional syncope in patients with AVS. The value of the EEC model is its ability to quantify the effect of a selective and gradable change in heart rate, ventricular contractility, or systemic vascular resistance on the hemodynamics during an exertional syncope in patients with severe AVS.

  2. Characterization of niphatenones that inhibit androgen receptor N-terminal domain.

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    Carmen A Banuelos

    Full Text Available Androgen ablation therapy causes a temporary reduction in tumor burden in patients with advanced prostate cancer. Unfortunately the malignancy will return to form lethal castration-recurrent prostate cancer (CRPC. The androgen receptor (AR remains transcriptionally active in CRPC in spite of castrate levels of androgens in the blood. AR transcriptional activity resides in its N-terminal domain (NTD. Possible mechanisms of continued AR transcriptional activity may include, at least in part, expression of constitutively active splice variants of AR that lack the C-terminal ligand-binding domain (LBD. Current therapies that target the AR LBD, would not be effective against these AR variants. Currently no drugs are clinically available that target the AR NTD which should be effective against these AR variants as well as full-length AR. Niphatenones were originally isolated and identified in active extracts from Niphates digitalis marine sponge. Here we begin to characterize the mechanism of niphatenones in blocking AR transcriptional activity. Both enantiomers had similar IC50 values of 6 µM for inhibiting the full-length AR in a functional transcriptional assay. However, (S-niphatenone had significantly better activity against the AR NTD compared to (R-niphatenone. Consistent with niphatenones binding to and inhibiting transactivation of AR NTD, niphatenones inhibited AR splice variant. Niphatenone did not affect the transcriptional activity of the related progesterone receptor, but slightly decreased glucocorticoid receptor (GR activity and covalently bound to GR activation function-1 (AF-1 region. Niphatenone blocked N/C interactions of AR without altering either AR protein levels or its intracellular localization in response to androgen. Alkylation with glutathione suggests that niphatenones are not a feasible scaffold for further drug development.

  3. Suppression of cell death by the secretory form of N-terminal ERC/mesothelin.

    Science.gov (United States)

    Wang, Tegexibaiyin; Kajino, Kazunori; Abe, Masaaki; Tan, Ke; Maruo, Masumi; Sun, Guodong; Hagiwara, Yoshiaki; Maeda, Masahiro; Hino, Okio

    2010-08-01

    ERC/mesothelin is highly expressed in malignant mesothelioma, pancreatic cancer, and ovarian cancer. It is cleaved to a 30 kDa N-terminal secretory form (N-ERC) and a 40 kDa C-terminal membranous form (C-ERC). Several functions have been reported for full-length ERC (full-ERC) and C-ERC/mesothelin, such as in cell adhesion and invasion, stimulation of cell proliferation, and the suppression of cell death. However, there have been no studies to date on the function of secretory N-ERC, despite the fact that it is abundantly secreted into the sera of mesothelioma patients. In this study, we investigated whether N-ERC could function as a secretory factor to stimulate tumor progression. Full-, N, or C-ERC was overexpressed in the human hepatocellular carcinoma cell line Huh7 that lacks endogenous expression of ERC/mesothelin. Changes in the rates of cell proliferation and cell death were determined, and the state of signal transducers was examined using various endpoints: total cell counts, trypan blue exclusion rate, BrdU incorporation rate, TUNEL assay, and the phosphorylation of ERK1/2 and Stat3. In cells overexpressing N-ERC, phosphorylation of ERK1/2 was enhanced and the rate of cell death decreased, leading to the increase of cell number. The culture medium containing the secretory N-ERC also had the activity to increase the number of cells. Our data suggested that one of the full-ERC functions reported previously was mediated by the secretory N-ERC.

  4. Investigating the DNA-binding ability of GATA-1-N-terminal zinc finger

    International Nuclear Information System (INIS)

    Wong, R.; Newton, A.; Crossley, M.; Mackay, J.

    2001-01-01

    Erythroid transcription factor GATA-1 interacts with both DNA and other proteins through its zinc finger domains (ZnFs). While it has been known for me time that the C-terminal ZnF binds DNA at GATA sites, only recently has it been observed that the N-terminal finger (NF) is capable of interacting with GATC sites. Further, a number of naturally occurring mutations in NF (V205M, G208S, R216Q, D218G) that lead to anaemia and thrombocytopenia have been identified. We are interested in characterising the NF-DNA interaction and determining the effects of mutation upon this interaction. Using nuclear magnetic resonance (NMR) spectroscopy, we have observed an interaction between recombinant NF and a 16-mer DNA duplex containing a core GATC sequence. This result forms the basis from which residues in NF involved in DNA binding can be identified, and work is being carried out to improve the quality of the NMR data with the aim of determining the solution structure of the NF-DNA complex. The DNA-binding affinity of both wild-type and mutant NFs mentioned above is also being investigated using isothermal titration calorimetry. These data suggest that the strength of the interaction between NF and the 16-mer DNA duplex is in the sub-micromolar range, and comparisons between the DNA-binding affinities of the NF mutants are being made. Together, these studies will help us to understand how GATA-1 acts as a transcriptional regulator and how mutations in NF domain of GATA-1 may lead to blood disorders

  5. Involvement of c-Jun N-Terminal Kinase in TNF-α-Driven Remodeling.

    Science.gov (United States)

    Eurlings, Irene M J; Reynaert, Niki L; van de Wetering, Cheryl; Aesif, Scott W; Mercken, Evi M; de Cabo, Rafael; van der Velden, Jos L; Janssen-Heininger, Yvonne M; Wouters, Emiel F M; Dentener, Mieke A

    2017-03-01

    Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is characterized by airway wall thickening and/or emphysema. Although the bronchial and alveolar compartments are functionally independent entities, we recently showed comparable alterations in matrix composition comprised of decreased elastin content and increased collagen and hyaluronan contents of alveolar and small airway walls. Out of several animal models tested, surfactant protein C (SPC)-TNF-α mice showed remodeling in alveolar and airway walls similar to what we observed in patients with COPD. Epithelial cells are able to undergo a phenotypic shift, gaining mesenchymal properties, a process in which c-Jun N-terminal kinase (JNK) signaling is involved. Therefore, we hypothesized that TNF-α induces JNK-dependent epithelial plasticity, which contributes to lung matrix remodeling. To this end, the ability of TNF-α to induce a phenotypic shift was assessed in A549, BEAS2B, and primary bronchial epithelial cells, and phenotypic markers were studied in SPC-TNF-α mice. Phenotypic markers of mesenchymal cells were elevated both in vitro and in vivo, as shown by the expression of vimentin, plasminogen activator inhibitor-1, collagen, and matrix metalloproteinases. Concurrently, the expression of the epithelial markers, E-cadherin and keratin 7 and 18, was attenuated. A pharmacological inhibitor of JNK attenuated this phenotypic shift in vitro, demonstrating involvement of JNK signaling in this process. Interestingly, activation of JNK signaling was also clearly present in lungs of SPC-TNF-α mice and patients with COPD. Together, these data show a role for TNF-α in the induction of a phenotypic shift in vitro, resulting in increased collagen production and the expression of elastin-degrading matrix metalloproteinases, and provide evidence for involvement of the TNF-α-JNK axis in extracellular matrix remodeling.

  6. N-terminal Slit2 inhibits HIV-1 replication by regulating the actin cytoskeleton

    Directory of Open Access Journals (Sweden)

    Anand Appakkudal R

    2013-01-01

    Full Text Available Abstract Background Slit2 is a ~ 200 kDa secreted glycoprotein that has been recently shown to regulate immune functions. However, not much is known about its role in HIV (human immunodeficiency virus-1 pathogenesis. Results In the present study, we have shown that the N-terminal fragment of Slit2 (Slit2N (~120 kDa inhibits replication of both CXCR4 and CCR5-tropic HIV-1 viruses in T-cell lines and peripheral blood T-cells. Furthermore, we demonstrated inhibition of HIV-1 infection in resting CD4+ T-cells. In addition, we showed that Slit2N blocks cell-to-cell transmission of HIV-1. We have shown that Slit2N inhibits HIV-1 infection by blocking viral entry into T-cells. We also ruled out Slit2N-mediated inhibition of various other steps in the life cycle including binding, integration and viral transcription. Elucidation of the molecular mechanism revealed that Slit2N mediates its functional effects by binding to Robo1 receptor. Furthermore, we found that Slit2N inhibited Gp120-induced Robo1-actin association suggesting that Slit2N may inhibit cytoskeletal rearrangements facilitating HIV-1 entry. Studies into the mechanism of inhibition of HIV-1 revealed that Slit2N abrogated HIV-1 envelope-induced actin cytoskeletal dynamics in both T-cell lines and primary T-cells. We further showed that Slit2N specifically attenuated the HIV-1 envelope-induced signaling pathway consisting of Rac1, LIMK and cofilin that regulates actin polymerization. Conclusions Taken together, our results show that Slit2N inhibits HIV-1 replication through novel mechanisms involving modulation of cytoskeletal dynamics. Our study, thus, provides insights into the role of Slit2N in HIV-1 infection and underscores its potential in limiting viral replication in T-cells.

  7. Autocatalytic activity and substrate specificity of the pestivirus N-terminal protease N{sup pro}

    Energy Technology Data Exchange (ETDEWEB)

    Gottipati, Keerthi; Acholi, Sudheer [Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555-0647 (United States); Ruggli, Nicolas [Institute of Virology and Immunology, CH-3147 Mittelhäusern (Switzerland); Choi, Kyung H., E-mail: kychoi@utmb.edu [Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, TX 77555-0647 (United States)

    2014-03-15

    Pestivirus N{sup pro} is the first protein translated in the viral polypeptide, and cleaves itself off co-translationally generating the N-terminus of the core protein. Once released, N{sup pro} blocks the host's interferon response by inducing degradation of interferon regulatory factor-3. N{sup pro'}s intracellular autocatalytic activity and lack of trans-activity have hampered in vitro cleavage studies to establish its substrate specificity and the roles of individual residues. We constructed N{sup pro}-GFP fusion proteins that carry the authentic cleavage site and determined the autoproteolytic activities of N{sup pro} proteins containing substitutions at the predicted catalytic sites Glu22 and Cys69, at Arg100 that forms a salt bridge with Glu22, and at the cleavage site Cys168. Contrary to previous reports, we show that N{sup pro'}s catalytic activity does not involve Glu22, which may instead be involved in protein stability. Furthermore, N{sup pro} does not have specificity for Cys168 at the cleavage site even though this residue is conserved throughout the pestivirus genus. - Highlights: • N{sup pro'}s autoproteolysis is studied using N{sup pro}-GFP fusion proteins. • N-terminal 17 amino acids are dispensable without loss of protease activity. • The putative catalytic residue Glu22 is not involved in protease catalysis. • No specificity for Cys168 at the cleavage site despite evolutionary conservation. • N{sup pro} prefers small amino acids with non-branched beta carbons at the P1 position.

  8. N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes.

    Directory of Open Access Journals (Sweden)

    Zenawit Girmatsion

    Full Text Available BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks and atrial fibrillation (a human arrhythmia. Structure-function relationship of the KCNE1 N-terminus for I(Ks modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA' were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Δ1-38'. Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks. Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex.

  9. End of NICE 95 and NICE NT services

    CERN Multimedia

    2003-01-01

    You are concerned by this article if you still use a computer running NICE 95 or NICE NT. As recommended by the Desktop Forum, NICE 95 and NT services will be stopped according to the following schedule: 31st January 2003: NICE 95/NT will be frozen. Applications will still be able to run, but the helpdesk will not address any NICE 95/NT problems anymore. It will not be possible to reinstall NICE 95/NT anymore. Disk images of the original Windows 95 and Windows NT CDs are available on the network, but it will be up to the user to create those CDs, reinstall the machine(s), as well as to locate and install: - the required applications, - the device drivers for special hardware, - the necessary security patches, - an anti-virus software (Operational Circular N 5 of CERN's Computing Rules (http://cern.ch/ComputingRules) requires that Windows PCs are regularly checked for viruses). The original Windows 95 and Windows NT CD images can be obtained from http://cern.ch/win/services/installation/CDImages (please ...

  10. END OF NICE 95 AND NICE NT SERVICES

    CERN Multimedia

    2002-01-01

    You are concerned by this article if you still use a computer running NICE 95 or NICE NT. As recommended by the Desktop Forum, NICE 95 and NT services will be stopped according to the following schedule: 31st January 2003: NICE 95/NT will be frozen. Applications will still be able to run, but the helpdesk will not address any NICE 95/NT problems anymore. It will not be possible to reinstall NICE 95/NT anymore. Disk images of the original Windows 95 and Windows NT CDs are available on the network, but it will be up to the user to create those CDs, reinstall the machine(s), as well as to locate and install: the required applications, the device drivers for special hardware, the necessary security patches, an anti-virus software (Operational Circular Nº5 of CERN's Computing Rules requires that Windows PCs are regularly checked for viruses). The original Windows 95 and Windows NT CD images can be obtained from http://cern.ch/win/services/installation/CDImages (please enter your NICE username and pa...

  11. End of NICE 95 and NICE NT services (Reminder)

    CERN Multimedia

    2003-01-01

    You are concerned by this article if you still use a computer running NICE 95 or NICE NT. As recommended by the Desktop Forum, NICE 95 and NT services are progressively phased out according to the following schedule: Since 31st January 2003: NICE 95/NT have been frozen. Applications are still able to run, but the helpdesk does not address any NICE 95/NT problems anymore. It is not possible to reinstall NICE 95/NT anymore. Disk images of the original Windows 95 and Windows NT CDs are available on the network, but it is up to the user to create those CDs, reinstall the machine(s), as well as to locate and install: - the required applications, - the device drivers for special hardware, - the necessary security patches, - an anti-virus software (Operational Circular N 5 of CERN's Computing Rules (http://cern.ch/ComputingRules) requires that Windows PCs are regularly checked for viruses). The original Windows 95 and Windows NT CD images can be obtained from http://cern.ch/win/services/installation/CDImages (ple...

  12. End of NICE 95 and NICE NT services

    CERN Multimedia

    2003-01-01

    You are concerned by this article if you still use a computer running NICE 95 or NICE NT. As recommended by the Desktop Forum, NICE 95 and NT services will be stopped according to the following schedule: 31st January 2003: NICE 95/NT will be frozen. Applications will still be able to run, but the helpdesk will not address any NICE 95/NT problems anymore. It will not be possible to reinstall NICE 95/NT anymore. Disk images of the original Windows 95 and Windows NT CDs are available on the network, but it will be up to the user to create those CDs, reinstall the machine(s), as well as to locate and install: - the required applications, - the device drivers for special hardware, - the necessary security patches, - an anti-virus software (Operational Circular N 5 of CERN's Computing Rules (http://cern.ch/ComputingRules) requires that Windows PCs are regularly checked for viruses). The original Windows 95 and Windows NT CD images can be obtained from http://cern.ch/win/services/installation/CDImages (please...

  13. N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Boesen, Mikael; Olsen, Michael

    2004-01-01

    and preserved LV function demonstrated that NT-proBNP was a very strong prognostic marker, especially combined with a history of cardiovascular disease. Patients with high NT-proBNP and known cardiovascular disease had a seven-fold increase in CV events compared to patients with low NT-proBNP and no CV disease......In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value.......47, P=0.0002) measured by magnetic resonance imaging. In other subjects with arterial hypertension a significant but weak correlation to diastolic properties has been demonstrated. As for prognosis, a recent study in patients with hypertension, electrocardiographic left ventricular hypertrophy...

  14. A review of guidelines and pharmacologic options for asthma treatment, with a focus on exercise-induced bronchoconstriction.

    Science.gov (United States)

    Spangler, Mikayla; Hawley, Heather; Barnes, Nicole; Saxena, Shailendra

    2013-09-01

    Asthma affects millions of individuals worldwide. Exercise-induced bronchoconstriction is common in patients diagnosed with asthma, but may also occur in patients without chronic asthma. Patients with isolated exercise-induced bronchoconstriction may require pretreatment with inhaled short-acting β-agonists prior to exercise. Patients diagnosed with asthma can achieve good control of the symptoms of exercise-induced bronchoconstriction with appropriate treatment of underlying chronic asthma. Current guidelines suggest staging patients with asthma based on severity of symptoms and initiating therapy according to their stage. Pharmacotherapy for asthma management consists of both quick-relief medications (short-acting β-agonists) as well as maintenance, or long-term control, medications (inhaled corticosteroids, long-acting β-agonists, leukotriene receptor antagonists, cromolyn, and theophylline).

  15. Prevalence and Associated Clinical Characteristics of Exercise-Induced ST-Segment Elevation in Lead aVR.

    Directory of Open Access Journals (Sweden)

    James McKinney

    Full Text Available Exercise-induced ST-segment elevation (STE in lead aVR may be an important indicator of prognostically important coronary artery disease (CAD. However, the prevalence and associated clinical features of exercise-induced STE in lead aVR among consecutive patients referred for exercise stress electrocardiography (ExECG is unknown.All consecutive patients receiving a Bruce protocol ExECG for the diagnosis of CAD at a tertiary care academic center were included over a two-year period. Clinical characteristics, including results of coronary angiography, were compared between patients with and without exercise-induced STE in lead aVR.Among 2227 patients undergoing ExECG, exercise-induced STE ≥1.0mm in lead aVR occurred in 3.4% of patients. Patients with STE in lead aVR had significantly lower Duke Treadmill Scores (DTS (-0.5 vs. 7.0, p<0.01 and a higher frequency of positive test results (60.2% vs. 7.3%, p<0.01. Furthermore, patients with STE in lead aVR were more likely to undergo subsequent cardiac catheterization than those without STE in lead aVR (p<0.01, odds ratio = 4.2.Among patients referred for ExECG for suspected CAD, exercise-induced STE in lead aVR was associated with a higher risk DTS, an increased likelihood of a positive ExECG, and referral for subsequent coronary angiography. These results suggest that exercise-induced STE in lead aVR may represent a useful ECG feature among patients undergoing ExECG in the risk stratification of patients.

  16. Structure of a double hexamer of the Pyrococcus furiosus minichromosome maintenance protein N-terminal domain

    Energy Technology Data Exchange (ETDEWEB)

    Meagher, Martin; Enemark, Eric J.

    2016-06-22

    The crystal structure of the N-terminal domain of thePyrococcus furiosusminichromosome maintenance (MCM) protein as a double hexamer is described. The MCM complex is a ring-shaped helicase that unwinds DNA at the replication fork of eukaryotes and archaea. Prior to replication initiation, the MCM complex assembles as an inactive double hexamer at specific sites of DNA. The presented structure is highly consistent with previous MCM double-hexamer structures and shows two MCM hexamers with a head-to-head interaction mediated by the N-terminal domain. Minor differences include a diminished head-to-head interaction and a slightly reduced inter-hexamer rotation.

  17. Exercise-Induced Laryngeal Obstruction and Performance Psychology: Using the Mind as a Diagnostic and Therapeutic Target.

    Science.gov (United States)

    Olin, J Tod; Westhoff Carlson, Erika

    2018-05-01

    Exercise-induced laryngeal obstruction causes severe shortness of breath during exercise. Episodes are associated with severe distress. These patients and those with inducible laryngeal obstruction triggered by other factors have been noted to demonstrate mental health disorders, personality features that may be associated with symptoms, and dysfunctional stress responses. This literature review calls attention to the observation that patients with isolated exercise-induced laryngeal obstruction are generally mentally healthy. We review available metrics to assess traits and stress responses in performance psychology. We also discuss a therapeutic performance psychology framework. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Interaction of the N-terminal segment of pulmonary surfactant protein SP-C with interfacial phospholipid films

    DEFF Research Database (Denmark)

    Plasencia, Inés; Keough, Kevin M W; Perez-Gil, Jesus

    2005-01-01

    Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine containing N-terminal segment. This segment is likely the only structural motif the protein projects out of the bilayer in which SP-C is ins...... related with the ability of SP-C to facilitate reinsertion of surface active lipid molecules into the lung interface during respiratory compression-expansion cycling. Udgivelsesdato: 2005-Jul-30...

  19. A novel calmodulin-regulated Ca2+-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain

    Science.gov (United States)

    Harper, J. F.; Hong, B.; Hwang, I.; Guo, H. Q.; Stoddard, R.; Huang, J. F.; Palmgren, M. G.; Sze, H.; Evans, M. L. (Principal Investigator)

    1998-01-01

    To study transporters involved in regulating intracellular Ca2+, we isolated a full-length cDNA encoding a Ca2+-ATPase from a model plant, Arabidopsis, and named it ACA2 (Arabidopsis Ca2+-ATPase, isoform 2). ACA2p is most similar to a "plasma membrane-type" Ca2+-ATPase, but is smaller (110 kDa), contains a unique N-terminal domain, and is missing a long C-terminal calmodulin-binding regulatory domain. In addition, ACA2p is localized to an endomembrane system and not the plasma membrane, as shown by aqueous-two phase fractionation of microsomal membranes. ACA2p was expressed in yeast as both a full-length protein (ACA2-1p) and an N-terminal truncation mutant (ACA2-2p; Delta residues 2-80). Only the truncation mutant restored the growth on Ca2+-depleted medium of a yeast mutant defective in both endogenous Ca2+ pumps, PMR1 and PMC1. Although basal Ca2+-ATPase activity of the full-length protein was low, it was stimulated 5-fold by calmodulin (50% activation around 30 nM). In contrast, the truncated pump was fully active and insensitive to calmodulin. A calmodulin-binding sequence was identified within the first 36 residues of the N-terminal domain, as shown by calmodulin gel overlays on fusion proteins. Thus, ACA2 encodes a novel calmodulin-regulated Ca2+-ATPase distinguished by a unique N-terminal regulatory domain and a non-plasma membrane localization.

  20. Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12.

    Science.gov (United States)

    Achenbach, Peter; Hawa, Mohammed I; Krause, Stephanie; Lampasona, Vito; Jerram, Samuel T; Williams, Alistair J K; Bonifacio, Ezio; Ziegler, Anette G; Leslie, R David

    2018-04-04

    Adult-onset type 1 diabetes, in which the 65 kDa isoform of GAD (GAD65) is a major autoantigen, has a broad clinical phenotype encompassing variable need for insulin therapy. This study aimed to evaluate whether autoantibodies against N-terminally truncated GAD65 more closely defined a type 1 diabetes phenotype associated with insulin therapy. Of 1114 participants with adult-onset diabetes from the Action LADA (latent autoimmune diabetes in adults) study with sufficient sera, we selected those designated type 1 (n = 511) or type 2 diabetes (n = 603) and retested the samples in radiobinding assays for human full-length GAD65 autoantibodies (f-GADA) and N-terminally truncated (amino acids 96-585) GAD65 autoantibodies (t-GADA). Individuals' clinical phenotypes were analysed according to antibody binding patterns. Overall, 478 individuals were f-GADA-positive, 431 were t-GADA-positive and 628 were negative in both assays. Risk of insulin treatment was augmented in t-GADA-positive individuals (OR 4.69 [95% CI 3.57, 6.17]) compared with f-GADA-positive individuals (OR 3.86 [95% CI 2.95, 5.06]), irrespective of diabetes duration. Of 55 individuals who were f-GADA-positive but t-GADA-negative, i.e. with antibody binding restricted to the N-terminus of GAD65, the phenotype was similar to type 2 diabetes with low risk of progression to insulin treatment. Compared with these individuals with N-terminal GAD65-restricted GADA, t-GADA-positive individuals were younger at diagnosis (p = 0.005), leaner (p N-terminally truncated GAD65 autoantibodies is associated with the clinical phenotype of autoimmune type 1 diabetes and predicts insulin therapy.

  1. Fine tuning of the catalytic activity of colicin E7 nuclease domain by systematic N-terminal mutations

    Czech Academy of Sciences Publication Activity Database

    Németh, E.; Körtvélyesi, T.; Thulstrup, P. W.; Christensen, H. E. M.; Kožíšek, Milan; Nagata, K.; Czene, A.; Gyurcsik, B.

    2014-01-01

    Roč. 23, č. 8 (2014), s. 1113-1122 ISSN 0961-8368 Grant - others:Seventh Framework Programme of the European Union(XE) FP7-312284; OPPC(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : DNA cleavage * flow linear dichroism * isothermal calorimetry * positively charged N-terminal residues * Zn2+ binding Subject RIV: CE - Biochemistry Impact factor: 2.854, year: 2014

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

    Science.gov (United States)

    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.

  3. Endothelial immunomediated reactivity in acute cardiac ischaemia: Role of endothelin 1, interleukin 8 and NT-proBNP in patients affected by unstable angina pectoris.

    Science.gov (United States)

    Caroselli, Costantino; De Rosa, Rosario; Tanzi, Pietro; Rigatelli, Alberto; Bruno, Guglielmo

    2016-09-01

    The role of endothelium in the progression of atheromasic disease has already been demonstrated. Endothelin-1 (ET-1) is released from endothelial cells during acute and chronic vascular damage and it appears to be the strongest vasoconstrictor agent known.The aim of this study is to investigate the amount of endothelial damage in patients with unstable angina (UA), as defined by serum levels of ET-1, to verify a possible correlation with increased ischaemic damage by evaluation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin 8 (IL-8) levels.Serum levels of ET-1, IL-8 and NT-proBNP obtained from 10 patients affected by low-risk UA were compared to those belonging to eight healthy subjects. In order to compare the laboratory data pertaining to the two populations, a Student's t-test and a Mann-Whitney U test were performed.Levels of ET-1, IL-8 and NT-proBNP in samples of peripheral blood of patients affected by UA were significantly elevated, compared with those of the control group. The linear correlation analysis demonstrated a positive and significant correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP in subjects affected by UA.Early elevated levels of ET-1, IL-8 and NT-proBNP in patients with UA show a coexistence between ischaemic insults and endothelial damages. A positive and significant linear correlation between levels of ET-1 and IL-8, between levels of ET-1 and NT-proBNP, and between levels of IL-8 and NT-proBNP confirms that an increased ischaemic insult is correlated to inflammation signs and endothelium damage signs.In patients with UA, ischaemia is always associated with a systemic immuno-mediated activity induced by acute endothelial damage. We suggest early administration of ET-1-selective receptor blockers and anti-inflammatory drugs. © The Author(s) 2015.

  4. Antigenic modules in the N-terminal S1 region of the transmissible gastroenteritis virus spike protein

    Science.gov (United States)

    Reguera, Juan; Ordoño, Desiderio; Santiago, César; Enjuanes, Luis

    2011-01-01

    The N-terminal S1 region of the transmissible gastroenteritis virus (TGEV) spike (S) glycoprotein contains four antigenic sites (C, B, D and A, from the N- to the C-terminal end) and is engaged in host-cell receptor recognition. The most N-terminal portion of the S1 region, which comprises antigenic sites C and B, is needed for the enteric tropism of TGEV, whereas the major antigenic site A at the C-terminal moiety is required for both respiratory and enteric cell tropism, and is engaged in recognition of the aminopeptidase N (APN) receptor. This study determined the kinetics for binding of a soluble S1 protein to the APN protein. Moreover, the S1 region of the TGEV S protein was dissected, with the aim of identifying discrete modules displaying unique antigenic sites and receptor-binding functions. Following protease treatments and mammalian cell expression methods, four modules or domains (D1–D4) were defined at the S1 region. Papain treatment identified an N-terminal domain (D1) resistant to proteolysis, whereas receptor binding defined a soluble and functional APN receptor-binding domain (D3). This domain was recognized by neutralizing antibodies belonging to the antigenic site A and therefore could be used as an immunogen for the prevention of viral infection. The organization of the four modules in the S1 region of the TGEV S glycoprotein is discussed. PMID:21228126

  5. The first N-terminal unprotected (Gly-Aib)n peptide: H-Gly-Aib-Gly-Aib-OtBu.

    Science.gov (United States)

    Gessmann, Renate; Brückner, Hans; Petratos, Kyriacos

    2015-12-01

    Glycine (Gly) is incorporated in roughly half of all known peptaibiotic (nonribosomally biosynthesized antibiotic peptides of fungal origin) sequences and is the residue with the greatest conformational flexibility. The conformational space of Aib (α-aminoisobutyric acid) is severely restricted by the second methyl group attached to the Cα atom. Most of the crystal structures containing Aib are N-terminal protected. Deprotection of the N- or C-terminus of peptides may alter the hydrogen-bonding scheme and/or the structure and may facilitate crystallization. The structure reported here for glycyl-α-aminoisobutyrylglycyl-α-aminoisobutyric acid tert-butyl ester, C16H30N4O5, describes the first N-terminal-unprotected (Gly-Aib)n peptide. The achiral peptide could form an intramolecular hydrogen bond between the C=O group of Gly1 and the N-H group of Aib4. This hydrogen bond is found in all tetrapeptides and N-terminal-protected tripeptides containing Aib, apart from one exception. In the present work, this hydrogen bond is not observed (N...O = 5.88 Å). Instead, every molecule is hydrogen bonded to six other symmetry-related molecules with a total of eight hydrogen bonds per molecule. The backbone conformation starts in the right-handed helical region (and the left-handed helical region for the inverted molecule) and reverses the screw sense in the last two residues.

  6. N-Terminal Coiled-Coil Structure of ATPase Subunits of 26S Proteasome Is Crucial for Proteasome Function

    Science.gov (United States)

    Inobe, Tomonao; Genmei, Reiko

    2015-01-01

    The proteasome is an essential proteolytic machine in eukaryotic cells, where it removes damaged proteins and regulates many cellular activities by degrading ubiquitinated proteins. Its heterohexameric AAA+ ATPase Rpt subunits play a central role in proteasome activity by the engagement of substrate unfolding and translocation for degradation; however, its detailed mechanism remains poorly understood. In contrast to AAA+ ATPase domains, their N-terminal regions of Rpt subunits substantially differ from each other. Here, to investigate the requirements and roles of the N-terminal regions of six Rpt subunits derived from Saccharomyces cerevisiae, we performed systematic mutational analysis using conditional knockdown yeast strains for each Rpt subunit and bacterial heterologous expression system of the base subcomplex. We showed that the formation of the coiled-coil structure was the most important for the N-terminal region of Rpt subunits. The primary role of coiled-coil structure would be the maintenance of the ring structure with the defined order. However, the coiled-coil region would be also be involved in substrate recognition and an interaction between lid and base subcomplexes. PMID:26208326

  7. Purification and antimicrobial activity studies of the N-terminal fragment of ubiquitin from human amniotic fluid.

    Science.gov (United States)

    Kim, Jin-Young; Lee, Sun Young; Park, Seong-Cheol; Shin, Song Yub; Choi, Sang Joon; Park, Yoonkyung; Hahm, Kyung-Soo

    2007-09-01

    A 4.3-kDa antimicrobial peptide was isolated from human amniotic fluid by dialysis, ultrafiltration, and C18 reversed-phase high performance liquid chromatography. This peptide, which we named Amniotic Fluid Peptide-1 (AFP-1), possessed antimicrobial activity but lacked hemolytic activity. In addition, AFP-1 potently inhibited the growth of a variety of bacteria (Escherichia coli, Salmonella typhimurium, Listeria monocytogenes and Staphylococcus aureus), filamentous fungi (Botrytis cinerea, Aspergillus fumigatus, Neurospora crassa and Fusarium oxysporum) and yeast cells (Candida albicans and Cryptococcus neoformans). Automated Edman degradation showed that the N-terminal sequence of AFP-1 was NH(2)-Met-Gln-Ile-Phe-Val-Lys-Thr-Leu-Thr-Gly-Lys-Thr-Ile-Thr-Leu-Glu-Val-Glu-. The partial sequence had 100% homology to the N-terminal sequence of ubiquitin. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry revealed that the molecular mass of AFP-1 was 4280.2 Da. Our data show an antimicrobial activity of ubiquitin N-terminal derived peptide that makes it suitable for use as an antimicrobial agent.

  8. ORF Alignment: NT_033779 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available n-like protein CL3 [Periplaneta americana] ... Length = 128 ... Query: 1 ... MVLDNQEDKLLTTTFLKSMGLSFTQSWHH... NT_033779 gi|21357645 >1qddA 26 143 127 254 1e-07 ... dbj|BAA82266.1| Cockroach lecti

  9. Exercise-induced bronchospasm in children with asthma in the United States: results from the Exercise-Induced Bronchospasm Landmark Survey.

    Science.gov (United States)

    Ostrom, Nancy K; Eid, Nemr S; Craig, Timothy J; Colice, Gene L; Hayden, Mary Lou; Parsons, Jonathan P; Stoloff, Stuart W

    2011-01-01

    Despite the availability of effective therapies, uncontrolled asthma remains a common problem. Previous large surveys suggest that exercise-related respiratory symptoms may be a significant element of uncontrolled asthma. The Exercise-Induced Bronchospasm (EIB) Landmark Survey is the first comprehensive, national survey evaluating EIB awareness and impact among the general public, asthma patients, and health care providers. This study was designed to evaluate the prevalence and impact of exercise-related respiratory symptoms in children (aged 4-17 years) with asthma. A national survey was conducted with parents of 516 children diagnosed with asthma or taking medications for asthma in the prior year. The majority of parents reported that their child experienced one or more exercise-related respiratory symptom and almost one-half (47.4%) experienced four or more symptoms. Most commonly reported symptoms were coughing, shortness of breath, and wheezing. Respondents reported that asthma limited their child's ability to participate either "a lot" or "some" in sports (30%), other outdoor activities (26.3%), and normal physical exertion (20.9%). Only 23.1% of children with exercise-related respiratory symptoms were reported to take short-acting beta-agonists such as albuterol "always" or "most of the time" before exercising. Exercise-related respiratory symptoms among pediatric asthma patients are common and substantially limit the ability of children to participate normally and perform optimally in physical activities. Such symptoms may reflect uncontrolled underlying asthma that should be evaluated and treated with appropriate controller medications. Despite the availability of preventative therapy, many children do not use short-acting bronchodilators before exercise as recommended in national guidelines.

  10. On the DAMA and CoGeNT Modulations

    DEFF Research Database (Denmark)

    Frandsen, Mads Toudal; Kahlhoefer, Felix; March-Russell, John

    2011-01-01

    DAMA observes an annual modulation in their event rate, as might be expected from dark matter scatterings, while CoGeNT has reported evidence for a similar modulation. The simplest interpretation of these findings in terms of dark matter-nucleus scatterings is excluded by other direct detection...... constraints, while inelasticity enhances the annual modulation fraction of the signal, bringing the CoGeNT and CDMS results into better agreement....

  11. Contribution of respiratory muscle blood flow to exercise-induced diaphragmatic fatigue in trained cyclists

    DEFF Research Database (Denmark)

    Vogiatzis, Ioannis; Athanasopoulos, Dimitris; Boushel, Robert Christopher

    2008-01-01

    We investigated whether the greater degree of exercise-induced diaphragmatic fatigue previously reported in highly trained athletes in hypoxia (compared with normoxia) could have a contribution from limited respiratory muscle blood flow. Seven trained cyclists completed three constant load 5 min...... exercise tests at inspired O(2) fractions (FIO2) of 0.13, 0.21 and 1.00 in balanced order. Work rates were selected to produce the same tidal volume, breathing frequency and respiratory muscle load at each FIO2 (63 +/- 1, 78 +/- 1 and 87 +/- 1% of normoxic maximal work rate, respectively). Intercostals...... and quadriceps muscle blood flow (IMBF and QMBF, respectively) were measured by near-infrared spectroscopy over the left 7th intercostal space and the left vastus lateralis muscle, respectively, using indocyanine green dye. The mean pressure time product of the diaphragm and the work of breathing did not differ...

  12. A Study To Assess The Prevalence Of Exercise-Induced Bronchoconstriction In Inter-County Hurling.

    LENUS (Irish Health Repository)

    Hunt, EB

    2017-11-01

    Exercise-Induced Bronchoconstriction (EIB) is an acute, transient airway narrowing occurring after exercise which may impact athletic performance. Studies report 10% of the general population and up to 90% of asthmatics experience EIB. Ninety-two players from three elite hurling squads underwent a spirometric field-based provocation test with real-time heart rate monitoring and lactate measurements to ensure adequate exertion. Players with a new diagnosis of EIB and those with a negative field-test but with a previous label of EIB or asthma underwent further reversibility testing and if negative, methacholine challenge. Eight (8.7%) of players had EIB, with one further athlete having asthma with a negative field test. Interestingly, only three out of 12 players who had previously been physician-labelled with EIB or asthma had their diagnosis objectively confirmed. Our study highlights the role of objective testing in EIB.

  13. Test-Retest Reliabilty of Exercise-Induced Hypoalgesia After Aerobic Exercise

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; Dørge, Daniel Bandholtz; Schmidt, Kristian Sonne

    2018-01-01

    Objective: Exercise increases pressure pain thresholds (PPTs) in exercising and nonexercising muscles, known as exercise-induced hypoalgesia (EIH). No studies have investigated the test-retest reliability of change in PPTs after aerobic exercise. Primary objectives were to compare the effect...... on PPTs after an incremental bicycling exercise compared with quiet rest and to investigate the relative and absolute test-retest reliability of the test stimulus (PPT) and the absolute and relative EIH response in exercising and nonexercising muscles. Setting: Laboratory. Methods: In two sessions, PPTs...... in the quadriceps and trapezius muscles were assessed before and after 15 minutes of quiet rest and 15 minutes of bicycling in 34 healthy subjects. Habitual physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Results: Bicycling increased PPTs in exercising and nonexercising...

  14. Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Hermansen, Mette N; Nielsen, Kim G

    2005-01-01

    BACKGROUND: Exercise-induced bronchoconstriction (EIB) is of particular importance in children with asthma. It is an important measure of asthma control and should be monitored by exercise testing. However, exercise testing puts a large demand on health-care resources and is therefore not widely...... to a standardized submaximal exercise test on the treadmill were measured in 111 school children with asthma. EIB could be excluded with a probability of 90% in asthmatic children with FeNO levels ... inhaled corticosteroid treatment. CONCLUSION: Measurement of FeNO is a simple, and time- and resource-efficient tool that may be used to screen for EIB testing and therefore optimizes the resources for exercise testing in pediatric asthma monitoring....

  15. Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

    DEFF Research Database (Denmark)

    Vægter, Henrik Bjarke; Handberg, Gitte; Graven-Nielsen, Thomas

    2014-01-01

    Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesised that the spatial and temporal manifestations of EIH and CPM were comparable. Eighty healthy subjects (40 females), between 18......-65 years participated in this randomized repeated-measures crossover trial with data collection on two different days. CPM was assessed by two different cold pressor tests (hand,foot). EIH was assessed through two intensities of aerobic bicycling exercises and two intensities of isometric muscle...... tests and after all of the exercise conditions, except low intensity bicycling. EIH after bicycling was increased in women compared to men. CPM and the EIH response after isometric exercises were comparable in men and women and not affected by age. The EIH response was larger in the exercising body part...

  16. Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans

    DEFF Research Database (Denmark)

    Møller, P; Loft, S; Lundby, C

    2001-01-01

    The present study investigated the effect of a single bout of exhaustive exercise on the generation of DNA strand breaks and oxidative DNA damage under normal conditions and at high-altitude hypoxia (4559 meters for 3 days). Twelve healthy subjects performed a maximal bicycle exercise test...... exercise in altitude hypoxia. Exercise-induced generation of DNA strand breaks was not seen at sea level. In both environments, the level of FPG and endonuclease III-sensitive sites remained unchanged immediately after exercise. DNA strand breaks and oxidative DNA damage are probably produced by reactive...... oxygen species, generated by leakage of the mitochondrial respiration or during a hypoxia-induced inflammation. Furthermore, the presence of DNA strand breaks may play an important role in maintaining hypoxia-induced inflammation processes. Hypoxia seems to deplete the antioxidant system of its capacity...

  17. L-arginine reduces exercise-induced increase in plasma lactate and ammonia.

    Science.gov (United States)

    Schaefer, A; Piquard, F; Geny, B; Doutreleau, S; Lampert, E; Mettauer, B; Lonsdorfer, J

    2002-08-01

    To investigate the effect of L-arginine supplementation (L-ARG) on physiological and metabolic changes during exercise, we determined in a double-blind study the cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal exercise after either an intravenous L-ARG hydrochloride salt or placebo load in 8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2) were not significantly different after L-ARG or placebo. By contrast, peak plasma ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2 vs. 73.1 +/- 9.1 micro mol x l(-1), p L-arginine-nitric oxide (NO) pathway during exercise.

  18. Effects of virtual reality-enhanced exercise equipment on adherence and exercise-induced feeling states.

    Science.gov (United States)

    Annesi, J J; Mazas, J

    1997-12-01

    A field study was conducted to test the effectiveness of virtual reality-enhanced cardiovascular exercise equipment for increasing adherence and attendance in a mixed-sex adult sample. Attendance was significantly higher in the virtual reality-enhanced condition than in the conditions without virtual reality over the 14-wk. period. Adherence was also highest (83.33%) in the virtual-reality bicycle group. Postexercise feelings of positive engagement, revitalization, tranquility, and physical exhaustion, as measured by the Exercise-induced Feeling Inventory, did not differ among groups. Contrary to previous findings, Self-motivation Inventory scores were not associated with either attendance or adherence. While findings suggest that virtual-reality features may promote exercise adherence or attendance, it is not yet known what psychological variables they affect. Implications were drawn regarding the practical possibilities for exercise promotion.

  19. Relative workload determines exercise-induced increases in PGC-1alpha mRNA

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai Baastrup; Lundby, Carsten; Leick, Lotte

    2010-01-01

    INTRODUCTION:: The hypothesis that brief intermittent exercise induced increases in human skeletal muscle metabolic mRNA is dependent on relative workload was investigated. METHODS:: Trained (n=10) and untrained (n=8) subjects performed exhaustive intermittent cycling exercise (4x4 min @ 85% of VO2...... peak, interspersed by 3 min). Trained subjects also performed the intermittent exercise at the same absolute workload as untrained, corresponding to 70% of VO2 peak (n=6). RESULTS:: Exercise at 85% of VO2 peak elevated (Ptrained...... after exercise at 85% of VO2 peak. Likewise, PDK4 and HKII mRNA expression were only increased (Ptrained subjects. HIF2alpha mRNA only increased (Ptrained, with no difference between the 70% and 85% of VO2 peak...

  20. Validity and reliability of grade scoring in the diagnosis of exercise-induced laryngeal obstruction

    DEFF Research Database (Denmark)

    Walsted, Emil Schwarz; Hull, James H; Hvedstrup, Jeppe

    2017-01-01

    The current gold-standard method for diagnosing exercise-induced laryngeal obstruction (EILO) is continuous laryngoscopy during exercise (CLE), with severity classified by a visual grade scoring system. We evaluated the precision of this approach, by evaluating test-retest reliability of CLE...... and both inter- and intra-rater variability. In this prospective case-control study, subjects completed four consecutive treadmill CLE tests under identical conditions. Laryngoscopic video recordings were anonymised and graded by three expert raters. 2 months following initial scoring, videos were re......-randomised and rating repeated to assess intra-rater agreement. 20 subjects (16 cases and four controls) completed four CLE tests. The time to exhaustion increased by 30 s (95% CI 0.02-57.8, ptest, but remained identical in the subsequent tests. Only one...

  1. N-Terminal Lipid Modification Is Required for the Stable Accumulation of CyanoQ in Synechocystis sp. PCC 6803.

    Directory of Open Access Journals (Sweden)

    Andrea D Juneau

    Full Text Available The CyanoQ protein has been demonstrated to be a component of cyanobacterial Photosystem II (PS II, but there exist a number of outstanding questions concerning its physical association with the complex. CyanoQ is a lipoprotein; upon cleavage of its transit peptide by Signal Peptidase II, which targets delivery of the mature protein to the thylakoid lumenal space, the N-terminal cysteinyl residue is lipid-modified. This modification appears to tether this otherwise soluble component to the thylakoid membrane. To probe the functional significance of the lipid anchor, mutants of the CyanoQ protein have been generated in Synechocystis sp. PCC 6803 to eliminate the N-terminal cysteinyl residue, preventing lipid modification. Substitution of the N-terminal cysteinyl residue with serine (Q-C22S resulted in a decrease in the amount of detectable CyanoQ protein to 17% that of the wild-type protein. Moreover, the physical properties of the accumulated Q-C22S protein were consistent with altered processing of the CyanoQ precursor. The Q-C22S protein was shifted to a higher apparent molecular mass and partitioned in the hydrophobic phase in TX-114 phase-partitioning experiments. These results suggest that the hydrophobic N-terminal 22 amino acids were not properly cleaved by a signal peptidase. Substitution of the entire CyanoQ transit peptide with the transit peptide of the soluble lumenal protein PsbO yielded the Q-SS mutant and resulted in no detectable accumulation of the modified CyanoQ protein. Finally, the CyanoQ protein was present at normal amounts in the PS II mutant strains ΔpsbB and ΔpsbO, indicating that an association with PS II was not a prerequisite for stable CyanoQ accumulation. Together these results indicate that CyanoQ accumulation in Synechocystis sp. PCC 6803 depends on the presence of the N-terminal lipid anchor, but not on the association of CyanoQ with the PS II complex.

  2. Effects of macro- and micronutrients on exercise-induced hepcidin response in highly trained endurance athletes.

    Science.gov (United States)

    Dahlquist, Dylan T; Stellingwerff, Trent; Dieter, Brad P; McKenzie, Donald C; Koehle, Michael S

    2017-10-01

    Iron deficiency has ergolytic effects on athletic performance. Exercise-induced inflammation impedes iron absorption in the digestive tract by upregulating the expression of the iron regulatory protein, hepcidin. Limited research indicates the potential of specific macro- and micronutrients on blunting exercise-induced hepcidin. Therefore, we investigated the effects of postexercise supplementation with protein and carbohydrate (CHO) and vitamins D 3 and K 2 on the postexercise hepcidin response. Ten highly trained male cyclists (age: 26.9 ± 6.4 years; maximal oxygen uptake: 67.4 ± 4.4 mL·kg -1 ·min -1 completed 4 cycling sessions in a randomized, placebo-controlled, single-blinded, triple-crossover study. Experimental days consisted of an 8-min warm-up at 50% power output at maximal oxygen uptake, followed by 8 × 3-min intervals at 85% power output at maximal oxygen uptake with 1.5 min at 60% power output at maximal oxygen uptake between each interval. Blood samples were collected pre- and postexercise, and at 3 h postexercise. Three different drinks consisting of CHO (75 g) and protein (25 g) with (VPRO) or without (PRO) vitamins D 3 (5000 IU) and K 2 (1000 μg), or a zero-calorie control drink (PLA) were consumed immediately after the postexercise blood sample. Results showed that the postexercise drinks had no significant (p ≥ 0.05) effect on any biomarker measured. There was a significant (p drink compositions used did not blunt the postexercise hepcidin response in highly trained athletes.

  3. Exercise-induced bronchospasm diagnosis in children. Utility of combined lung function tests.

    Science.gov (United States)

    Sánchez-García, Silvia; Rodríguez del Río, Pablo; Escudero, Carmelo; García-Fernández, Cristina; Ibáñez, Maria Dolores

    2015-02-01

    The diagnosis of exercise-induced asthma or bronchospasm (EIB) is a complex dare in daily clinical practice. The consensus is that if bronchial hyper-responsiveness (BHR) is demonstrated in a patient with symptoms consistent with EIB, then that patient can be diagnosed with exercise-induced bronchospasm. The aim of this study was to determine which BHR test is the most efficient to diagnose EIB. Children under 16, without previous asthma diagnosis, or with stable asthma, complaining of asthma-like symptoms triggered by exercise were included. Bronchodilator, methacholine, mannitol, and exercise tests were performed on all patients, following established protocols. The performance of single and combined tests was determined. Of 46 patients (median age: 12 yr, ranged 8-16 y.o.) were recruited, 30 (70%) previously diagnosed of asthma. BHR was detected in 93.47% of the children. The exercise challenge test detected BHR in 11 of 46 (23.90%) patients, bronchodilator test in 10 of 46 (21.70%), mannitol in 36 of 45 (80%) and methacholine in 41 of 45 (91.11%). The total number of patients with BHR was detected using a combination of the methacholine and mannitol tests. A combination of the methacholine test performed first, followed by the mannitol test, was able to diagnose BHR in 100% of children with lower number of tests (n = 45) than if the order was reversed (n = 50). Methacholine and mannitol tests detect BHR in most children with suspected EIB. Bronchodilator and exercise tests show a low positivity rate. A combination of the methacholine test, followed by the mannitol test, gives the highest return to identify BHR in children for the diagnosis of EIB. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

    Science.gov (United States)

    Walsted, Emil S; Faisal, Azmy; Jolley, Caroline J; Swanton, Laura L; Pavitt, Matthew J; Luo, Yuan-Ming; Backer, Vibeke; Polkey, Michael I; Hull, James H

    2018-02-01

    Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P laryngeal closure ( P laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal

  5. Exercise-induced blood lactate increase does not change red blood cell deformability in cyclists.

    Directory of Open Access Journals (Sweden)

    Michael J Simmonds

    Full Text Available BACKGROUND: The effect of exercise-induced lactate production on red blood cell deformability and other blood rheological changes is controversial, given heavy-exercise induces biochemical processes (e.g., oxidative stress known to perturb haemorheology. The aim of the present study was to examine the haemorheological response to a short-duration cycling protocol designed to increase blood lactate concentration, but of duration insufficient to induce significant oxidative stress. METHODS: Male cyclists and triathletes (n = 6; 27±7 yr; body mass index: 23.7±3.0 kg/m²; peak oxygen uptake 4.02±0.51 L/min performed unloaded (0 W, moderate-intensity, and heavy-intensity cycling. Blood was sampled at rest and during the final minute of each cycling bout. Blood chemistry, blood viscosity, red blood cell aggregation and red blood cell deformability were measured. RESULTS: Blood lactate concentration increased significantly during heavy-intensity cycling, when compared with all other conditions. Methaemoglobin fraction did not change during any exercise bout when compared with rest. Blood viscosity at native haematocrit increased during heavy-intensity cycling at higher-shear rates when compared with rest, unloaded and moderate-intensity cycling. Heavy-intensity exercise increased the amplitude of red blood cell aggregation in native haematocrit samples when compared with all other conditions. Red blood cell deformability was not changed by exercise. CONCLUSION: Acute exercise perturbs haemorheology in an intensity dose-response fashion; however, many of the haemorheological effects appear to be secondary to haemoconcentration, rather than increased lactate concentration.

  6. Effects of Massage on Muscular Strength and Proprioception After Exercise-Induced Muscle Damage.

    Science.gov (United States)

    Shin, Mal-Soon; Sung, Yun-Hee

    2015-08-01

    Exercise-induced muscle damage (EIMD), which is commonly associated with eccentric exercise, unaccustomed exercise, and resistance training, may lead to delayed onset muscle soreness, swelling, decreased muscle strength, and range of motion. Many researchers have evaluated various interventions to treat the signs and symptoms of EIMD. However, the effects of massage after EIMD are unclear. Here, we investigated the effect of massage on muscle strength and proprioception after EIMD. All subjects randomly were divided into an EIMD-treated control group (n = 10) and a massage-treated after EIMD experimental group (n = 11). Exercise-induced muscle damage was induced by repeated exercise. Massage treatment was provided by physiotherapist for 15 minutes. It consists of light stroking, milking, friction, and skin rolling. Lactate was evaluated by Lactate Pro analyzer in pre- and postexercise. Surface electromyography (muscle activity) and sonography (muscle thickness) were used to confirm the muscular characteristics. Proprioception was investigated by dual inclinometer. As a result, massage treatment on the gastrocnemius after EIMD increased activation of the medial gastrocnemius during contraction (p ≤ 0.05). In the lateral and medial gastrocnemius, the θs, which is the angle between muscle fibers and superficial aponeurosis, showed a significant change (p ≤ 0.05). However, there are no differences in the θd, which is the angle between muscle fibers and deep aponeurosis. We also found that proprioceptive acuity in the ankle joint was significantly greater in the massage-treated experimental group compared with that in the control group (p ≤ 0.05). These findings suggest that massage of the gastrocnemius after EIMD can improve muscle strength and proprioception by influencing the superficial layer of the gastrocnemius.

  7. Exercise-induced albuminuria and circadian blood pressure abnormalities in type 2 diabetes

    Science.gov (United States)

    Tankeu, Aurel T; Kaze, François Folefack; Noubiap, Jean Jacques; Chelo, David; Dehayem, Mesmin Yefou; Sobngwi, Eugene

    2017-01-01

    AIM To investigate the relationship between circadian variations in blood pressure (BP) and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes (T2D) patients. METHODS We conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical proteinuria and normal creatinine clearance. In each participant, we recorded the BP using ambulatory blood pressure monitoring (ABPM) for 24-h, and albuminuria at rest and after a standardized treadmill exercise. RESULTS We enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure (SBP) of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg (P = 0.004), and mean diurnal diastolic blood pressure (DBP) of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg (P = 0.002). There was a significant difference between albuminuria at rest [median = 23 mg, interquartile range (IQR) = 10-51] and after exercise (median = 35 mg, IQR = 23-80, P albuminuria had an increase in nocturnal BP values on all three components (128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure), as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP (83 vs 86, P = 0.03) than resting albuminuria. CONCLUSION Exercise induced albuminuria is associated with an increase in nocturnal BP values in T2D patients. PMID:28729969

  8. Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression.

    Science.gov (United States)

    Zuhl, Micah N; Lanphere, Kathryn R; Kravitz, Len; Mermier, Christine M; Schneider, Suzanne; Dokladny, Karol; Moseley, Pope L

    2014-01-15

    The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P supplementation prevented exercise-induced permeability, possibly through HSF-1 activation.

  9. Occlusion of blood flow attenuates exercise-induced hypoalgesia in the occluded limb of healthy adults.

    Science.gov (United States)

    Jones, Matthew D; Taylor, Janet L; Barry, Benjamin K

    2017-05-01

    Animal studies have demonstrated an important role of peripheral mechanisms as contributors to exercise-induced hypoalgesia (EIH). Whether these same mechanisms contribute to EIH in humans is not known. In the current study, pain thresholds were assessed in healthy volunteers ( n = 36) before and after 5 min of high-intensity leg cycling exercise and an equivalent period of quiet rest. Pressure pain thresholds (PPTs) were assessed over the rectus femoris muscle of one leg and first dorsal interosseous muscles (FDIs) of both arms. Blood flow to one arm was occluded by a cuff throughout the 5-min period of exercise (or rest) and postexercise (or rest) assessments. Ratings of pain intensity and pain unpleasantness during occlusion were also measured. Pain ratings during occlusion increased over time (range, 1.5 to 3.5/10, all d > 0.63, P exercise conditions ( d 0.4). PPTs at all sites were unchanged following rest (range, -1.3% to +0.9%, all d 0.51). Consistent with EIH, exercise significantly increased PPT at the leg (+29%, d = 0.69, P exercise attenuates EIH, suggesting that peripheral factors contribute to EIH in healthy adults. NEW & NOTEWORTHY This is the first demonstration in humans that a factor carried by the circulation and acting at the periphery is important for exercise-induced hypoalgesia. Further understanding of this mechanism may provide new insight to pain relief with exercise as well as potential interactions between analgesic medications and exercise. Copyright © 2017 the American Physiological Society.

  10. Alleviating exercise-induced muscular stress using neat and processed bee pollen: oxidative markers, mitochondrial enzymes, and myostatin expression in rats

    Directory of Open Access Journals (Sweden)

    Sameer Ketkar

    2015-09-01

    Conclusion: The study establishes the antioxidant, mitochondrial upregulatory, and myostatin inhibitory effects of both MIMBP and PMIMBP in exercise-induced oxidative stress conditions, suggesting their usefulness in effective management of exercise-induced muscular stress. Further, processing of MIMBP with an edible lipid-surfactant mixture was found to improve the therapeutic efficiency of pollen.

  11. The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat

    DEFF Research Database (Denmark)

    Martins, Cecilia; Kulseng, B; King, N A

    2010-01-01

    The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic ...

  12. Relation between exercise-induced hypertension and sustained hypertension in adult patients after successful repair of aortic coarctation

    NARCIS (Netherlands)

    Vriend, Joris W. J.; van Montfrans, Gert A.; Romkes, Hans H.; Vliegen, Hubert W.; Veen, Gerrit; Tijssen, Jan G. P.; Mulder, Barbara J. M.

    2004-01-01

    Objectives To investigate whether exercise-induced hypertension in successfully repaired adult post-coarctectomy patients is associated with hypertension on 24-h blood pressure measurement and increased left ventricular mass. Methods One hundred and forty-four consecutive postcoarctectomy patients

  13. Prevalence of exercise-induced left ventricular outflow tract obstruction in symptomatic patients with non-obstructive hypertrophic cardiomyopathy.

    LENUS (Irish Health Repository)

    Shah, J S

    2008-10-01

    Resting left ventricular outflow tract obstruction (LVOTO) occurs in 25% of patients with hypertrophic cardiomyopathy (HCM) and is an important cause of symptoms and disease progression. The prevalence and clinical significance of exercise induced LVOTO in patients with symptomatic non-obstructive HCM is uncertain.

  14. The Free-Running Asthma Screening Test: An Approach to Screening for Exercise-Induced Asthma in Rural Alabama.

    Science.gov (United States)

    Heaman, Doris J.; Estes, Jenny

    1997-01-01

    This study documented the prevalence of exercise-induced asthma (EIA) in rural elementary schools, examining the use of a free-running asthma screening test and peak expiratory flow-rate measurement for school screening. Results indicated that 5.7% of the students had EIA. Absenteeism and poverty were related to EIA. (SM)

  15. A Systematic Review of the Literature on Screening for Exercise-Induced Asthma: Considerations for School Nurses

    Science.gov (United States)

    Worrell, Kelly; Shaw, Michele R.; Postma, Julie; Katz, Janet R.

    2015-01-01

    Asthma is a major cause of illness, missed school days, and hospitalization in children. One type of asthma common in children is exercise-induced asthma (EIA). EIA causes airway narrowing with symptoms of cough and shortness of breath during exercise. The purpose of this article is to review the literature relevant to screening children and…

  16. Angiopoietin-like protein 4 is an exercise-induced hepatokine in humans, regulated by glucagon and cAMP

    Directory of Open Access Journals (Sweden)

    Bodil Ingerslev

    2017-10-01

    Conclusions: The data suggest that exercise-induced ANGPTL4 is secreted from the liver and driven by a glucagon-cAMP-PKA pathway in humans. These findings link the liver, insulin/glucagon, and lipid metabolism together, which could implicate a role of ANGPTL4 in metabolic diseases.

  17. ABNORMAL PLASMA NORADRENALINE RESPONSE AND EXERCISE INDUCED ALBUMINURIA IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

    NARCIS (Netherlands)

    HOOGENBERG, K; DULLAART, RPF

    1992-01-01

    Submaximal exercise provokes an abnormal elevation in albuminuria in type 1 (insulin-dependent) diabetes mellitus. Plasma catecholamines might be involved in this phenomenon by a renal vasoconstrictive effect. Twelve healthy subjects (Controls: albuminuria It is concluded that the exercise-induced

  18. The Impact of Central and Peripheral Cyclooxygenase Enzyme Inhibition on Exercise-Induced Elevations in Core Body Temperature.

    NARCIS (Netherlands)

    Veltmeijer, M.T.W.; Veeneman, D.; Bongers, C.C.W.G.; Netea, M.G.; Meer, J.W.M. van der; Eijsvogels, T.M.H.; Hopman, M.T.E.

    2017-01-01

    PURPOSE: Exercise increases core body temperature (TC) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 (IL-6) may also contribute to the rise in TC by increasing the hypothalamic temperature set point. This study investigated

  19. A unique spumavirus Gag N-terminal domain with functional properties of orthoretroviral matrix and capsid.

    Directory of Open Access Journals (Sweden)

    David C Goldstone

    2013-05-01

    Full Text Available The Spumaretrovirinae, or foamyviruses (FVs are complex retroviruses that infect many species of monkey and ape. Although FV infection is apparently benign, trans-species zoonosis is commonplace and has resulted in the isolation of the Prototypic Foamy Virus (PFV from human sources and the potential for germ-line transmission. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. In addition, PFV Gag interacts with the FV Envelope (Env protein to facilitate budding of infectious particles. Presently, there is a paucity of structural information with regards FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. Therefore, in order to probe the functional overlap of FV and orthoretroviral Gag and learn more about FV egress and replication we have undertaken a structural, biophysical and virological study of PFV-Gag. We present the crystal structure of a dimeric amino terminal domain from PFV, Gag-NtD, both free and in complex with the leader peptide of PFV Env. The structure comprises a head domain together with a coiled coil that forms the dimer interface and despite the shared function it is entirely unrelated to either the capsid or matrix of Gag from other retroviruses. Furthermore, we present structural, biochemical and virological data that reveal the molecular details of the essential Gag-Env interaction and in addition we also examine the specificity of Trim5α restriction of PFV. These data provide the first information with regards to FV structural proteins and suggest a model for convergent evolution of gag genes where structurally unrelated molecules have become functionally equivalent.

  20. A unique spumavirus Gag N-terminal domain with functional properties of orthoretroviral matrix and capsid.

    Science.gov (United States)

    Goldstone, David C; Flower, Thomas G; Ball, Neil J; Sanz-Ramos, Marta; Yap, Melvyn W; Ogrodowicz, Roksana W; Stanke, Nicole; Reh, Juliane; Lindemann, Dirk; Stoye, Jonathan P; Taylor, Ian A

    2013-05-01

    The Spumaretrovirinae, or foamyviruses (FVs) are complex retroviruses that infect many species of monkey and ape. Although FV infection is apparently benign, trans-species zoonosis is commonplace and has resulted in the isolation of the Prototypic Foamy Virus (PFV) from human sources and the potential for germ-line transmission. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. In addition, PFV Gag interacts with the FV Envelope (Env) protein to facilitate budding of infectious particles. Presently, there is a paucity of structural information with regards FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. Therefore, in order to probe the functional overlap of FV and orthoretroviral Gag and learn more about FV egress and replication we have undertaken a structural, biophysical and virological study of PFV-Gag. We present the crystal structure of a dimeric amino terminal domain from PFV, Gag-NtD, both free and in complex with the leader peptide of PFV Env. The structure comprises a head domain together with a coiled coil that forms the dimer interface and despite the shared function it is entirely unrelated to either the capsid or matrix of Gag from other retroviruses. Furthermore, we present structural, biochemical and virological data that reveal the molecular details of the essential Gag-Env interaction and in addition we also examine the specificity of Trim5α restriction of PFV. These data provide the first information with regards to FV structural proteins and suggest a model for convergent evolution of gag genes where structurally unrelated molecules have become functionally equivalent.

  1. Value of NT-ProBNP level and echocardiographic parameters in ST-segment elevation myocardial infarction treated by primary angioplasty: relationships between these variables and their usefulness as predictors of ventricular remodeling.

    Science.gov (United States)

    López Haldón, José; Fernández Quero, Mónica; Mancha, Fernando; Urbano, José A; Guisado, Agustín; Villa, Manuel; Valle, Juan I; Rodríguez Puras, María J; Ballesteros, Sara; López Pardo, Francisco; Díaz de la Llera, Luis; Sánchez González, Angel; Martínez Martínez, Angel

    2010-09-01

    To assess the value of N-terminal fragment of brain natriuretic peptide (NT-proBNP) measurement and echocardiography for predicting ventricular remodeling after myocardial infarction and to investigate relationships between the NT-proBNP level and echocardiographic parameters at discharge and in the medium term. The study involved 159 patients with myocardial infarction treated by primary coronary angioplasty. The NT-proBNP level was measured on admission, at discharge and after 6 months. Echocardiography was performed at discharge and after 6 months. Overall, 31 patients (19.5%) demonstrated remodeling. At discharge, the variables associated with remodeling were: mitral inflow E-wave-to-A-wave velocity ratio (E/A), systolic mitral annulus velocity (Sm), early diastolic mitral annulus velocity (Em), the mitral inflow E wave to early diastolic mitral annulus velocity ratio (E/ Em), left atrial volume (LAV), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and discharge NT-proBNP level. Only E/Em was an independent predictor of ventricular remodeling (odds ratio [OR]=1.143; 95% confidence interval [CI], 1.039-1.258; P=.006). At discharge, correlations were observed between the NT-proBNP level and LVEDV, LVESV, ejection fraction (EF) and E/Em. At 6 months, correlations with ventricular volumes and EF were unchanged, the correlation with E/Em was better (r=0.47 vs. r=0.69), and a modest correlation with LAV developed (r=0.43; P=.001). The E/Em ratio was the best echocardiographic predictor of left ventricular remodeling after myocardial infarction. The NT-proBNP level had no additional predictive value over echocardiography. Correlations between the NT-proBNP level and ventricular volumes and EF at discharge and 6 months were similar, while correlations with E/Em and LAV were better at 6 months.

  2. X-ray crystal structure of the N-terminal region of Moloney murine leukemia virus integrase and its implications for viral DNA recognition: N-Terminal Region of M-MuLV Integrase

    Energy Technology Data Exchange (ETDEWEB)

    Guan, Rongjin [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Aiyer, Sriram [Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Cote, Marie L. [Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway New Jersey 08854; Xiao, Rong [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Jiang, Mei [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Acton, Thomas B. [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Roth, Monica J. [Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Montelione, Gaetano T. [Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway New Jersey 08854; Department of Biochemistry, Robert Wood Johnson Medical School, UMDNJ, Piscataway New Jersey 08854

    2017-02-03

    The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain, and the C-terminal domain. The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1–44) and an HHCC zinc-finger NTD (residues 45–105), in two crystal forms are reported. The structures of IN NTR constructs encoding residues 1–105 (NTR1–105) and 8–105 (NTR8–105) were determined at 2.7 and 2.15 Å resolution, respectively and belong to different space groups. While both crystal forms have similar protomer structures, NTR1–105 packs as a dimer and NTR8–105 packs as a tetramer in the asymmetric unit. The structure of the NED consists of three anti-parallel β-strands and an α-helix, similar to the NED of prototype foamy virus (PFV) IN. These three β-strands form an extended β-sheet with another β-strand in the HHCC Zn2+ binding domain, which is a unique structural feature for the M-MuLV IN. The HHCC Zn2+ binding domain structure is similar to that in HIV and PFV INs, with variations within the loop regions. Differences between the PFV and MLV IN NEDs localize at regions identified to interact with the PFV LTR and are compared with established biochemical and virological data for M-MuLV. Proteins 2017; 85:647–656.

  3. Prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients without coronary artery disease.

    Science.gov (United States)

    Prada-Delgado, Oscar; Barge-Caballero, Eduardo; Peteiro, Jesús; Bouzas-Mosquera, Alberto; Estévez-Loureiro, Rodrigo; Barge-Caballero, Gonzalo; López-Pérez, Manuel; Vázquez-González, Nicolás; Castro-Beiras, Alfonso

    2015-02-01

    We sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients with normal resting echocardiography and absence of coronary artery disease. From our database of patients referred for treadmill exercise echocardiography, we identified 93 hypertensive patients with preserved resting left ventricular ejection fraction (≥ 50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 39 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 54 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. Patients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95%CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). In hypertensive patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  4. Adding serial N-terminal pro brain natriuretic peptide measurements to optimal clinical management in outpatients with systolic heart failure

    DEFF Research Database (Denmark)

    Schou, Morten; Gustafsson, Finn; Videbaek, Lars

    2013-01-01

    management (n = 208) or clinical management + NT-proBNP monitoring (n = 199) and followed for 2.5 years. If NT-proBNP increased >30%, a clinical checklist was completed and treatment initiated. The patients were matched at randomization and were 73 years old, 25% were females, 85% were NYHA class I-II, LVEF.......009), and a lower quality of life (P = 0.032) and a poorer functional class (37% vs. 18% in NYHA class III-IV, P clinical management was not associated with a change in pharmacological strategy and did not improve outcome......AIMS: This study was designed to evaluate a new NT-proBNP monitoring concept in outpatients with systolic heart failure (HF). METHODS AND RESULTS: This was a multicentre, prospective randomized open-label blinded endpoint study. A total of 407 systolic HF patients were allocated to either clinical...

  5. 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...

  6. The influence of anaemia on stroke prognosis and its relation to N-terminal pro-brain natriuretic peptide

    DEFF Research Database (Denmark)

    Nybo, M; Kristensen, S R; Mickley, H

    2007-01-01

    the prevalence of renal affection, smoking and heart failure was lower. At 6 months follow-up, 23 patients were dead, and anaemia had an odds ratio of 4.7 when adjusted for age, Scandinavian Stroke Scale and a combined variable of heart and/or renal failure and/or elevation of troponin T using logistic...... regression. The median NT-proBNP level in the anaemic group was significantly higher than in the non-anaemic group, and in a multivariate linear regression model, anaemia remained an independent predictor of NT-proBNP. Conclusively, anaemia was found to be a negative prognostic factor for ischemic stroke...

  7. HYDRAULICS AND MIXING EVALUATIONS FOR NT-21/41 TANKS

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.; Barnes, O.

    2014-11-17

    The hydraulic results demonstrate that pump head pressure of 20 psi recirculates about 5.6 liters/min flowrate through the existing 0.131-inch orifice when a valve connected to NT-41 is closed. In case of the valve open to NT-41, the solution flowrates to HB-Line tanks, NT-21 and NT-41, are found to be about 0.5 lpm and 5.2 lpm, respectively. The modeling calculations for the mixing operations of miscible fluids contained in the HB-Line tank NT-21 were performed by taking a three-dimensional Computational Fluid Dynamics (CFD) approach. The CFD modeling results were benchmarked against the literature results and the previous SRNL test results to validate the model. Final performance calculations were performed for the nominal case by using the validated model to quantify the mixing time for the HB-Line tank. The results demonstrate that when a pump recirculates a solution volume of 5.7 liters every minute out of the 72-liter tank contents containing two acid solutions of 2.7 M and 0 M concentrations (i.e., water), a minimum mixing time of 1.5 hours is adequate for the tank contents to get the tank contents adequately mixed. In addition, the sensitivity results for the tank contents of 8 M existing solution and 1.5 M incoming species show that the mixing time takes about 2 hours to get the solutions mixed.

  8. Linear flow dynamics near a T/NT interface

    Science.gov (United States)

    Teixeira, Miguel; Silva, Carlos

    2011-11-01

    The characteristics of a suddenly-inserted T/NT interface separating a homogeneous and isotropic shear-free turbulence region from a non-turbulent flow region are investigated using rapid distortion theory (RDT), taking full account of viscous effects. Profiles of the velocity variances, TKE, viscous dissipation rate, turbulence length scales, and pressure statistics are derived, showing very good agreement with DNS. The normalized inviscid flow statistics at the T/NT interface do not depend on the form of the assumed TKE spectrum. In the non-turbulent region, where the flow is irrotational (except within a thin viscous boundary layer), the dissipation rate decays as z-6, where z is distance from the T/NT interface. The mean pressure exhibits a decrease towards the turbulence due to the associated velocity fluctuations, consistent with the generation of a mean entrainment velocity. The vorticity variance and dissipation rate display large maxima at the T/NT interface due to the existing inviscid discontinuities of the tangential velocity, and these maxima are quantitatively related to the thickness of the viscous boundary layer (VBL). At equilibrium, RDT suggests that the thickness of the T/NT interface scales on the Kolmogorov microscale. We acknowledge the financial support of FCT under Project PTDC/EME-MFE/099636/2008.

  9. Phosphorylation Regulates Interaction of 210-kDa Myosin Light Chain Kinase N-terminal Domain with Actin Cytoskeleton.

    Science.gov (United States)

    Vilitkevich, E L; Khapchaev, A Y; Kudryashov, D S; Nikashin, A V; Schavocky, J P; Lukas, T J; Watterson, D M; Shirinsky, V P

    2015-10-01

    High molecular weight myosin light chain kinase (MLCK210) is a multifunctional protein involved in myosin II activation and integration of cytoskeletal components in cells. MLCK210 possesses actin-binding regions both in the central part of the molecule and in its N-terminal tail domain. In HeLa cells, mitotic protein kinase Aurora B was suggested to phosphorylate MLCK210 N-terminal tail at serine residues (Dulyaninova, N. G., and Bresnick, A. R. (2004) Exp. Cell Res., 299, 303-314), but the functional significance of the phosphorylation was not established. We report here that in vitro, the N-terminal actin-binding domain of MLCK210 is located within residues 27-157 (N27-157, avian MLCK210 sequence) and is phosphorylated by cAMP-dependent protein kinase (PKA) and Aurora B at serine residues 140/149 leading to a decrease in N27-157 binding to actin. The same residues are phosphorylated in a PKA-dependent manner in transfected HeLa cells. Further, in transfected cells, phosphomimetic mutants of N27-157 showed reduced association with the detergent-stable cytoskeleton, whereas in vitro, the single S149D mutation reduced N27-157 association with F-actin to a similar extent as that achieved by N27-157 phosphorylation. Altogether, our results indicate that phosphorylation of MLCK210 at distinct serine residues, mainly at S149, attenuates the interaction of MLCK210 N-terminus with the actin cytoskeleton and might serve to regulate MLCK210 microfilament cross-linking activity in cells.

  10. Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis.

    Science.gov (United States)

    Feng, Han-Zhong; Biesiadecki, Brandon J; Yu, Zhi-Bin; Hossain, M Moazzem; Jin, J-P

    2008-07-15

    The N-terminal variable region of cardiac troponin T (TnT) is a regulatory structure that can be selectively removed during myocardial ischaemia reperfusion by mu-calpain proteolysis. Here we investigated the pathophysiological significance of this post-translational modification that removes amino acids 1-71 of cardiac TnT. Working heart preparations were employed to study rat acute myocardial infarction and transgenic mouse hearts over-expressing the N-terminal truncated cardiac TnT (cTnT-ND). Ex vivo myocardial infarction by ligation of the left anterior descending coronary artery induced heart failure and produced cTnT-ND not only in the infarct but also in remote zones, including the right ventricular free wall, indicating a whole organ response in the absence of systemic neurohumoral mechanisms. Left ventricular pressure overload in mouse working hearts produced increased cTnT-ND in both ventricles, suggesting a role of haemodynamic stress in triggering an acute whole organ proteolytic regulation. Transgenic mouse hearts in which the endogenous intact cardiac TnT was partially replaced by cTnT-ND showed lowered contractile velocity. When afterload increased from 55 mmHg to 90 mmHg, stroke volume decreased in the wild type but not in the transgenic mouse hearts. Correspondingly, the left ventricular rapid-ejection time of the transgenic mouse hearts was significantly longer than that of wild type hearts, especially at high afterload. The restricted deletion of the N-terminal variable region of cardiac troponin T demonstrates a novel mechanism by which the thin filament regulation adapts to sustain cardiac function under stress conditions.

  11. Affects of N-terminal variation in the SeM protein of Streptococcus equi on antibody and fibrinogen binding.

    Science.gov (United States)

    Timoney, John F; DeNegri, Rafaela; Sheoran, Abhineet; Forster, Nathalie

    2010-02-10

    The clonal Streptococcus equi causes equine strangles, a highly contagious suppurative lymphadenopathy and rhinopharyngitis. An important virulence factor and vaccine component, the antiphagocytic fibrinogen binding SeM of S. equi is a surface anchored fibrillar protein. Two recent studies of N. American, Japanese and European isolates have revealed a high frequency of N-terminal amino acid variation in SeM of S. equi CF32 that suggests this region of the protein is subject to immunologic selection pressure. The aims of the present study were firstly to map regions of SeM reactive with convalescent equine IgG and IgA and stimulatory for lymph node cells and secondly to determine effects of N-terminal variation on the functionality of SeM. Variation did not significantly affect fibrinogen binding or susceptibility of S. equi to an opsonic equine serum. Linear epitopes reactive with convalescent IgG and mucosal IgA were concentrated toward the conserved center of SeM. However, IgA but not IgG from every horse reacted with at least one peptide that contained variable sequence. Lymph node cells (CD4+) from horses immunized with SeM were strongly responsive to a peptide (alphaalpha36-138) encoding the entire variable region. SeM (CF32) specific mouse Mab 04D11 which reacted strongly with this larger peptide but not with shorter peptides within that sequence reacted strongly with whole cells of S. equi CF32 but only weakly with cells of any of 14 isolates of S. equi expressing different variants of SeM. These results in combination suggest that N-terminal variation alters a conformational epitope of significance in mucosal IgA and systemic T cell responses but does not affect antibody mediated phagocytosis and killing. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  12. Functional Analysis of γ-Tubulin Complex Proteins Indicates Specific Lateral Association via Their N-terminal Domains.

    Science.gov (United States)

    Farache, Dorian; Jauneau, Alain; Chemin, Cécile; Chartrain, Marine; Rémy, Marie-Hélène; Merdes, Andreas; Haren, Laurence

    2016-10-28

    Microtubules are nucleated from multiprotein complexes containing γ-tubulin and associated γ-tubulin complex proteins (GCPs). Small complexes (γTuSCs) comprise two molecules of γ-tubulin bound to the C-terminal domains of GCP2 and GCP3. γTuSCs associate laterally into helical structures, providing a structural template for microtubule nucleation. In most eukaryotes γTuSCs associate with additional GCPs (4, 5, and 6) to form the core of the so-called γ-tubulin ring complex (γTuRC). GCPs 2-6 constitute a family of homologous proteins. Previous structural analysis and modeling of GCPs suggest that all family members can potentially integrate into the helical structure. Here we provide experimental evidence for this model. Using chimeric proteins in which the N- and C-terminal domains of different GCPs are swapped, we show that the N-terminal domains define the functional identity of GCPs, whereas the C-terminal domains are exchangeable. FLIM-FRET experiments indicate that GCP4 and GCP5 associate laterally within the complex, and their interaction is mediated by their N-terminal domains as previously shown for γTuSCs. Our results suggest that all GCPs are incorporated into the helix via lateral interactions between their N-terminal domains, whereas the C-terminal domains mediate longitudinal interactions with γ-tubulin. Moreover, we show that binding to γ-tubulin is not essential for integrating into the helical complex. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Conserved N-terminal negative charges support optimally efficient N-type inactivation of Kv1 channels.

    Directory of Open Access Journals (Sweden)

    Alison Prince

    Full Text Available N-type inactivation is produced by the binding of a potassium channel's N-terminus within the open pore, blocking conductance. Previous studies have found that introduction of negative charges into N-terminal inactivation domains disrupts inactivation; however, the Aplysia AKv1 N-type inactivation domain contains two negatively charged residues, E2 and E9. Rather than being unusual, sequence analysis shows that this N-terminal motif is highly conserved among Kv1 sequences across many phyla. Conservation analysis shows some tolerance at position 9 for other charged residues, like D9 and K9, whereas position 2 is highly conserved as E2. To examine the functional importance of these residues, site directed mutagenesis was performed and effects on inactivation were recorded by two electrode voltage clamp in Xenopus oocytes. We find that inclusion of charged residues at positions 2 and 9 prevents interactions with non-polar sites along the inactivation pathway increasing the efficiency of pore block. In addition, E2 appears to have additional specific electrostatic interactions that stabilize the inactivated state likely explaining its high level of conservation. One possible explanation for E2's unique importance, consistent with our data, is that E2 interacts electrostatically with a positive charge on the N-terminal amino group to stabilize the inactivation domain at the block site deep within the pore. Simple electrostatic modeling suggests that due to the non-polar environment in the pore in the blocked state, even a 1 Å larger separation between these charges, produced by the E2D substitution, would be sufficient to explain the 65× reduced affinity of the E2D N-terminus for the pore. Finally, our studies support a multi-step, multi-site N-type inactivation model where the N-terminus interacts deep within the pore in an extended like structure placing the most N-terminal residues 35% of the way across the electric field in the pore blocked

  14. Barley polyamine oxidase: Characterisation and analysis of the cofactor and the N-terminal amino acid sequence

    DEFF Research Database (Denmark)

    Radova, A.; Sebela, M.; Galuszka, P.

    2001-01-01

    was further purified to a final homogeneity (by the criteria of isoelectric focusing and SDS-PAGE) using techniques of low pressure chromatography followed by two FPLC steps. The purified yellow enzyme showed visible absorption maxima of a flavoprotein at 380 and 450 nm: the presence of FAD as the cofactor...... was further confirmed by measuring the fluorescence spectra, Barley PAO is an acidic protein (pI 5.4) containing 3% of neutral sugars: its molecular mass determined by SDS-PAGE was 56 kDa, whilst gel permeation chromatography revealed the higher value of 76 kDa. The N-terminal amino acid sequence of barley...

  15. Mutational analysis of Escherichia coli elongation factor Tu in search of a role for the N-terminal region

    DEFF Research Database (Denmark)

    Mansilla, Francisco; Knudsen, Charlotte Rohde; Laurberg, M

    1998-01-01

    We have mutated lysine 2 and arginine 7 in elongation factor Tu from Escherichia coli separately either to alanine or glutamic acid. The aim of the work was to reveal the possible interactions between the conserved N-terminal part of the molecule, which is rich in basic residues and aminoacyl...... this activity. Furthermore, arginine 7 seems to play a role in regulating the binding of GTP. The three-dimensional structure of the ternary complex, EF-Tu:GTP:Phe-tRNAPhe, involving Thermus aquaticus EF-Tu and yeast Phe-tRNA(Phe), shows that Arg7 is in a position which permits salt bridge formation with Asp284...

  16. Isolation of three allergenic fractions of the major allergen from Olea europea pollen and N-terminal amino acid sequence.

    Science.gov (United States)

    Villalba, M; López-Otín, C; Martín-Orozco, E; Monsalve, R I; Palomino, P; Lahoz, C; Rodríguez, R

    1990-10-30

    A method to isolate the major allergen from olive pollen (Ole e I) in high yield is described. The allergenic fraction has been separated into 3 subfractions by reverse-phase HPLC. All these fractions were reactive to allergic sera from olive-sensitized patients, giving similar responses. No significant differences were observed between the amino acid compositions of these three proteins. The amino acid sequence of the first 27 amino acid residues from the N-terminal end is given. No homologies have been detected between Ole e I and other known allergens obtained from pollen.

  17. Exercise-induced mobilisation of endothelial progenitor cells in patients with premature coronary heart disease.

    Science.gov (United States)

    Kaźmierski, Maciej; Wojakowski, Wojciech; Michalewska-Włudarczyk, Aleksandra; Podolecka, Ewa; Kotowski, Maciej; Machaliński, Bogusław; Tendera, Michał

    2015-01-01

    Endothelial progenitor cells (EPC) derive from bone marrow and participate in both endothelial regeneration and development of new blood vessels. EPC also play a role in the atherosclerotic process, and their number correlates negatively with the presence of classical risk factors. To evaluate circulating EPC count and their exercise-induced mobilisation in patients with premature coronary artery disease (CAD). The study group included 60 patients with stable CAD diagnosed before 45 years of age. The control group consisted of 33 healthy age- and gender-matched volunteers. Venous blood was sampled 3 times in order to assess circulating EPC count immediately before an exercise test (EPC 0) and at 15 min (EPC 15) and 60 min (EPC 60) after the exercise test. Circulating EPC count in the study group at rest and at 15 min after exercise was comparable (2.1 vs. 2.1 cell/μL, p = 0.35) and increased significantly at 60 min after exercise in comparison to resting values (2.1 vs. 3.2 cell/μL, p exercise (2.0 vs. 3.5 cell/μL, p exercise, although it remained greater than at rest (2.7 vs. 2.0 cell/μL, p exercise was comparable in the two groups (2.1 vs. 2.0 cell/μL, p = 0.96; and 3.2 vs. 2.7 cell/μL, p = 0.13, respectively) but it was significantly lower in the study group compared to the control group at 15 min after exercise (2.1 vs. 3.5 cell/μL, p exercise did not correlate with the number of stenosed coronary arteries but at 60 min after exercise it was greater in patients with one-vessel disease compared to those with two- or three-vessel disease (4.2 vs. 3.4 cell/μL, p = 0.01; and 4.2 vs. 2.3 cell/μL, p = 0.00003). However, no difference in circulating EPC count was seen at 60 min after exercise between patients with two- or three-vessel disease (3.4 vs. 2.3 cell/μL, p = 0.3). 1. Circulating EPC count at rest is comparable between subjects with premature atherosclerosis and healthy volunteers. 2. A single bout of physical exercise causes a significant increase

  18. Analysis of the distribution of charged residues in the N-terminal region of signal sequences: implications for protein export in prokaryotic and eukaryotic cells.

    OpenAIRE

    von Heijne, G

    1984-01-01

    A statistical analysis of the distribution of charged residues in the N-terminal region of 39 prokaryotic and 134 eukaryotic signal sequences reveals a remarkable similarity between the two samples, both in terms of net charge and in terms of the position of charged residues within the N-terminal region, and suggests that the formyl group on Metf is not removed in prokaryotic signal sequences.

  19. The cytoprotective role of taurine in exercise-induced muscle injury.

    Science.gov (United States)

    Dawson, R; Biasetti, M; Messina, S; Dominy, J

    2002-06-01

    Intense exercise is thought to increase oxidative stress and damage muscle tissue. Taurine is present in high concentration in skeletal muscle and may play a role in cellular defenses against free radical-mediated damage. The aim of this study was to determine if manipulating muscle levels of taurine would alter markers of free radical damage after exercise-induced injury. Adult male Sprague-Dawley rats were supplemented via the drinking water with either 3% (w/v) taurine (n = 10) or the competitive taurine transport inhibitor, beta-alanine (n = 10), for one month. Controls (n = 20) drank tap water containing 0.02% taurine and all rats were placed on a taurine free diet. All the rats except one group of sedentary controls (n = 10) were subjected to 90 minutes of downhill treadmill running. Markers of cellular injury and free radical damage were determined along with tissue amino acid content. The 3% taurine treatment raised plasma levels about 2-fold and 3% beta-alanine reduced plasma taurine levels about 50%. Taurine supplementation (TS) significantly increased plasma glutamate levels in exercised rats. Exercise reduced plasma methionine levels and taurine prevented its decline. Taurine supplementation increased muscle taurine content significantly in all muscles except the soleus. beta-alanine decreased muscle taurine content about 50% in all the muscles examined. Lipid peroxidation (TBARS) was significantly increased by exercise in the extensor digitorium longus (EDL) and gastrocnemius (GAST) muscles. Both taurine and beta-alanine completely blocked the increase in TBARs in the EDL, but had no effect in the GAST. Muscle content of the cytosolic enzyme, lactate dehydrogenase (LDH) was significantly decreased by exercise in the GAST muscle and this effect was attenuated by both taurine and beta-alanine. Muscle myeloperoxidase (MPO) activity was significantly elevated in the gastrocnemius muscle, but diet had no effect. MPO activity was significantly increased by

  20. Myosin Light Chain Kinase (MLCK Gene Influences Exercise Induced Muscle Damage during a Competitive Marathon.

    Directory of Open Access Journals (Sweden)

    Juan Del Coso

    Full Text Available Myosin light chain kinase (MLCK phosphorylates the regulatory light chain (RLC of myosin producing increases in force development during skeletal muscle contraction. It has been suggested that MLCK gene polymorphisms might alter RLC phosphorylation thereby decreasing the ability to produce force and to resist strain during voluntary muscle contractions. Thus, the genetic variations in the MLCK gene might predispose some individuals to higher values of muscle damage during exercise, especially during endurance competitions. The aim of this investigation was to determine the influence of MLCK genetic variants on exercise-induced muscle damage produced during a marathon. Sixty-seven experienced runners competed in a marathon race. The MLCK genotype (C37885A of these marathoners was determined. Before and after the race, a sample of venous blood was obtained to assess changes in serum myoglobin concentrations and leg muscle power changes were measured during a countermovement jump. Self-reported leg muscle pain and fatigue were determined by questionnaires. A total of 59 marathoners (88.1% were CC homozygotes and 8 marathoners (11.9% were CA heterozygotes. The two groups of participants completed the race with a similar time (228 ± 33 vs 234 ± 39 min; P = 0.30 and similar self-reported values for fatigue (15 ± 2 vs 16 ± 2 A.U.; P = 0.21 and lower-limb muscle pain (6.2 ± 1.7 vs 6.6 ± 1.8 cm; P = 0.29. However, CC marathoners presented higher serum myoglobin concentrations (739 ± 792 vs 348 ± 144 μg·mL-1; P = 0.03 and greater pre-to-post- race leg muscle power reduction (-32.7 ± 15.7 vs -21.2 ± 21.6%; P = 0.05 than CA marathoners. CA heterozygotes for MLCK C37885A might present higher exercise-induced muscle damage after a marathon competition than CC counterparts.

  1. High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial

    Directory of Open Access Journals (Sweden)

    Castaneda-Sceppa Carmen

    2011-04-01

    Full Text Available Abstract Background Inadequate energy intake induces changes in endogenous glucose production (GP to preserve muscle mass. Whether addition provision of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced energy deficit effects on glucose metabolism are mitigated by increased dietary protein. Methods Nineteen men ([mean ± SD] 23 ± 2 y, VO2peak 59 ± 5 ml·kg-1·min-1 were divided into three groups, two consuming moderate (MP; 0.9 g protein kg-1 d-1, and one high (HP; 1.8 g protein kg-1 d-1 protein diets (55% energy from carbohydrate for 11 days. Following 4 days of energy balance (D1-4, energy expenditure was increased for 7 days (D5-12 in all groups. Energy intake was unchanged in two, creating a 1000 kcal d-1 deficit (DEF-MP, DEF-HP; n = 6, both groups, whereas energy balance was maintained in the third (BAL-MP, n = 7. Biochemical markers of substrate metabolism were measured during fasting rest on D4 and D12, as were GP and contribution of gluconeogenesis to endogenous glucose production (fgng using 4-h primed, continuous infusions of [6,6-2H2]glucose (dilution-method and [2-13C]glycerol (MIDA technique. Glycogen breakdown (GB was derived from GP and fgng. Results Plasma β-hydroxybutyrate levels increased, and plasma glucose and insulin declined from D4 to D12, regardless of group. DEF-MP experienced decreased plasma GP from D4 to D12 ([mean change ± SD] 0.24 ± 0.24 mg·kg-1·min-1, due to reduced GB from D4 (1.40 ± 0.28 mg·kg-1·min-1 to D12 (1.16 ± 0.17 mg·kg-1·min-1, P -1·min-1, respectively by maintaining GB. Conclusion Exercise-induced energy deficit decreased GP and additional dietary protein mitigated that effect.

  2. Curcumin and Piperine Supplementation and Recovery Following Exercise Induced Muscle Damage: A Randomized Controlled Trial

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    Barthélémy Delecroix, Abd Elbasset Abaïdia, Cédric Leduc, Brian Dawson, Grégory Dupont

    2017-03-01

    Full Text Available The aim of this study was to analyze the effects of oral consumption of curcumin and piperine in combination on the recovery kinetics after exercise-induced muscle damage. Forty-eight hours before and following exercise-induced muscle damage, ten elite rugby players consumed curcumin and piperine (experimental condition or placebo. A randomized cross-over design was performed. Concentric and isometric peak torque for the knee extensors, one leg 6 seconds sprint performance on a non-motorized treadmill, counter movement jump performance, blood creatine kinase concentration and muscle soreness were assessed immediately after exercise, then at 24h, 48h and 72h post-exercise. There were moderate to large effects of the exercise on the concentric peak torque for the knee extensors (Effect size (ES = -1.12; Confidence interval at 90% (CI90%: -2.17 to -0.06, the one leg 6 seconds sprint performance (ES=-1.65; CI90% = -2.51to -0.80 and the counter movement jump performance (ES = -0.56; CI90% = -0.81 to -0.32 in the 48h following the exercise. There was also a large effect of the exercise on the creatine kinase level 72h after the exercise in the control group (ES = 3.61; CI90%: 0.24 to 6.98. This decrease in muscle function and this elevation in creatine kinase indicate that the exercise implemented was efficient to induce muscle damage. Twenty four hours post-exercise, the reduction (from baseline in sprint mean power output was moderately lower in the experimental condition (-1.77 ± 7.25%; 1277 ± 153W in comparison with the placebo condition (-13.6 ± 13.0%; 1130 ± 241W (Effect Size = -1.12; Confidence Interval 90%=-1.86 to -0.86. However, no other effect was found between the two conditions. Curcumin and piperine supplementation before and after exercise can attenuate some, but not all, aspects of muscle damage.

  3. Exercise-induced changes in left ventricular global longitudinal strain in asymptomatic severe aortic stenosis.

    Science.gov (United States)

    Lech, Agnieszka K; Dobrowolski, Piotr P; Klisiewicz, Anna; Hoffman, Piotr

    2017-01-01

    The management of patients with asymptomatic severe aortic stenosis (ASAS) is still under discussion. Therefore, it is advisable to search for the parameters of early damage to left ventricular (LV) function. The aim of the study was to assess exercise-induced changes in LV global longitudinal strain (GLS) in ASAS. The ASAS group consisted of 50 patients (26 women and 24 men, aged 38.4 ± 18.1 years) meeting the echocardiographic criteria of severe aortic stenosis (AVA 4 m/s, mean aortic gradient > 40 mm Hg), with normal LV ejection fraction (LVEF ≥ 55%) and sinus rhythm on electrocardiogram, and without significant concomitant valvular heart diseases. The control group consisted of 21 people matched for age and sex. Echocardiographic examinations and echocardiographic stress tests with the assessment of GLS using the speckle tracking imaging were performed. The ASAS group was characterised by statistically significantly higher LV mass index (LVMI) and higher LVEF. GLS values at rest in both groups were within normal limits but were significantly higher in the control group (-18.9 ± 2.4% vs. -20.7 ± 1.7%, p = 0.006). An increase in GLS at peak exercise in both groups was observed, lower in the ASAS group (the difference was not statistically significant: -0.8 ± 3.0% vs. -2.2 ± 3.1%, p = 0.086). Changes in GLS during exercise (ΔGLS) did not correlate with the parameters of the severity of aortic stenosis. In the multivariate model, LVMI proved to be a factor associated with GLS at rest and during exercise. In patients with ASAS, GLS is a non-invasive marker of an early stage of LV myocardial damage associated with myocardial hypertrophy. An increase in GLS during exercise in the ASAS group, smaller than in the control group, indicates a preserved functional reserve of the LV myocardium but smaller than in healthy individuals. The assessment of the clinical usefulness of exercise-induced changes in GLS requires further research.

  4. The effect of atenolol on NT-proBNP and troponin in asymptomatic cats with severe left ventricular hypertrophy because of hypertrophic cardiomyopathy: a pilot study.

    Science.gov (United States)

    Jung, S W; Kittleson, M D

    2011-01-01

    Atenolol often is used empirically in cats with hypertrophic cardiomyopathy (HCM) before the onset of heart failure, although evidence of efficacy is lacking. Cardiac biomarkers play a critical role in the early detection of subclinical cardiac disease, in the prediction of long-term prognosis, and in monitoring the response to therapy in humans. Circulating concentrations of the biomarkers N-terminal pro-B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) will decrease after chronic administration of atenolol PO to cats with severe HCM but no signs of heart failure. Six Maine Coon or Maine Coon cross cats with severe HCM. Cats were treated with atenolol (12.5 mg PO q12 h) for 30 days. No cat had left ventricular dynamic outflow tract obstruction caused by systolic anterior motion of the mitral valve. The concentrations of NT-proBNP and cTnI were assayed before and on the last day of drug administration. There was no statistically significant change in NT-proBNP (median before, 394 pmol/L; range, 71-1,500 pmol/L; median after, 439 pmol/L; range, 24-1,500 pmol/L; P = .63) or in cTnI (median before, 0.24 ng/mL; range, 0.10-0.97 ng/mL; median after, 0.28 ng/mL; range, 0.09-1.0 ng/mL; P = .69) after administration of atenolol. Atenolol administration did not decrease NT-proBNP or cTnI concentrations in cats with severe left ventricular hypertrophy caused by hypertrophic cardiomyopathy. These results suggest that atenolol did not decrease myocardial ischemia and myocyte death in these cats. A larger clinical trial is warranted to verify these findings. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  5. Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma

    International Nuclear Information System (INIS)

    Papazisis, Konstantinos T; Kortsaris, Alexandros H; Kontovinis, Lukas F; Papandreou, Christos N; Kouvatseas, George; Lafaras, Christos; Antonakis, Evangelos; Christopoulou, Maria; Andreadis, Charalambos; Mouratidou, Despoina

    2010-01-01

    Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients. We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma. From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001). This is the first time that a potential 'surrogate marker' has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice

  6. Linked production of pyroglutamate-modified proteins via self-cleavage of fusion tags with TEV protease and autonomous N-terminal cyclization with glutaminyl cyclase in vivo.

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    Yan-Ping Shih

    Full Text Available Overproduction of N-terminal pyroglutamate (pGlu-modified proteins utilizing Escherichia coli or eukaryotic cells is a challenging work owing to the fact that the recombinant proteins need to be recovered by proteolytic removal of fusion tags to expose the N-terminal glutaminyl or glutamyl residue, which is then converted into pGlu catalyzed by the enzyme glutaminyl cyclase. Herein we describe a new method for production of N-terminal pGlu-containing proteins in vivo via intracellular self-cleavage of fusion tags by tobacco etch virus (TEV protease and then immediate N-terminal cyclization of passenger target proteins by a bacterial glutaminyl cyclase. To combine with the sticky-end PCR cloning strategy, this design allows the gene of target proteins to be efficiently inserted into the expression vector using two unique cloning sites (i.e., SnaB I and Xho I, and the soluble and N-terminal pGlu-containing proteins are then produced in vivo. Our method has been successfully applied to the production of pGlu-modified enhanced green fluorescence protein and monocyte chemoattractant proteins. This design will facilitate the production of protein drugs and drug target proteins that possess an N-terminal pGlu residue required for their physiological activities.

  7. N-Terminal Domains in Two-Domain Proteins Are Biased to Be Shorter and Predicted to Fold Faster Than Their C-Terminal Counterparts

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    Etai Jacob

    2013-04-01

    Full Text Available Computational analysis of proteomes in all kingdoms of life reveals a strong tendency for N-terminal domains in two-domain proteins to have shorter sequences than their neighboring C-terminal domains. Given that folding rates are affected by chain length, we asked whether the tendency for N-terminal domains to be shorter than their neighboring C-terminal domains reflects selection for faster-folding N-terminal domains. Calculations of absolute contact order, another predictor of folding rate, provide additional evidence that N-terminal domains tend to fold faster than their neighboring C-terminal domains. A possible explanation for this bias, which is more pronounced in prokaryotes than in eukaryotes, is that faster folding of N-terminal domains reduces the risk for protein aggregation during folding by preventing formation of nonnative interdomain interactions. This explanation is supported by our finding that two-domain proteins with a shorter N-terminal domain are much more abundant than those with a shorter C-terminal domain.

  8. Expression, crystallization and preliminary X-ray data analysis of NT-Als9-2, a fungal adhesin from Candida albicans

    International Nuclear Information System (INIS)

    Salgado, Paula S.; Yan, Robert; Rowan, Fiona; Cota, Ernesto

    2011-01-01

    Details of the expression and crystallization of the N-terminal fragment of Als9-2, an adhesin from the human commensal/pathogenic fungus C. albicans, are reported. Preliminary analysis of the collected X-ray data is also discussed. Candida albicans is a common human fungal commensal that can also cause a range of infections from skin/mucosal ‘thrush’ to severe systemic candidiasis. Adherence to host cells is one of the key determinants of Candida pathogenesis. The Als family of surface proteins has been implicated in adhesion of C. albicans, yet limited information has been published on the structure and mechanism of these fungal adhesins. The N-terminal region of these proteins has been shown to possess adhesive properties, making it a possible target for new therapeutic strategies. Recombinant NT-Als9-2 from C. albicans (residues 18–329) was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.0 Å resolution. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 34.73, b = 68.71, c = 120.03 Å, α = β = γ = 90° and one molecule in the asymmetric unit. Platinum-derivatized crystals belonged to the same space group, with similar unit-cell parameters, although they were not completely isomorphous

  9. Characterization of the part of N-terminal PIP2 binding site of the TRPM1 channel.

    Science.gov (United States)

    Jirku, Michaela; Bumba, Ladislav; Bednarova, Lucie; Kubala, Martin; Sulc, Miroslav; Franek, Miloslav; Vyklicky, Ladislav; Vondrasek, Jiri; Teisinger, Jan; Bousova, Kristyna

    2015-12-01

    Transient receptor potential melastatin-1 (TRPM1) is a calcium channel that is essential for the depolarization of photo-responsive retinal bipolar cells, but most of the physiological functions and cellular roles of this channel are still poorly understood. Most transient receptor potential (TRP) channels are typically regulated by intracellular proteins and other signaling molecules. Phosphatidylinositol-4,5 bisphosphate (PIP2), a minor phospholipid component of cell membranes, has previously been shown to directly bind TRP channels and to play a unique role in modulating receptor function. To characterize the binding of PIP2 as a potential regulator of TRPM1, we utilized biophysical methods and molecular modeling to study the interactions of PIP2 with an N-terminal fragment of TRPM1 (residues A451-N566). The basic N-terminal residue K464 of TRPM1 suggests that it is part of putative pleckstrin homology (PH) domain and is involved in the interactions with PIP2. This is the first report detailing the binding of PIP2 at the N-terminus of the TRPM1 receptor. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. The role of the N-terminal loop in the function of the colicin E7 nuclease domain

    DEFF Research Database (Denmark)

    Czene, Anikó; Németh, Eszter; Zóka, István G.

    2013-01-01

    Colicin E7 (ColE7) is a metallonuclease toxin of Escherichia coli belonging to the HNH superfamily of nucleases. It contains highly conserved amino acids in its HHX14NX8HX3H ββα-type metal ion binding C-terminal active centre. However, the proximity of the arginine at the N-terminus of the nuclease...... domain of ColE7 (NColE7, 446–576) is necessary for the hydrolytic activity. This poses a possibility of allosteric activation control in this protein. To obtain more information on this phenomenon, two protein mutants were expressed, i.e. four and 25 N-terminal amino acids were removed from NColE7....... The effect of the N-terminal truncation on the Zn2+ ion and DNA binding as well as on the activity was investigated in this study by mass spectrometry, synchrotron-radiation circular dichroism and fluorescence spectroscopy and agarose gel mobility shift assays. The dynamics of protein backbone movement...

  11. The Dahlia mosaic virus gene VI product N-terminal region is involved in self-association.

    Science.gov (United States)

    Raikhy, Gaurav; Krause, Charles; Leisner, Scott

    2011-07-01

    The genome of the floriculture pathogen Dahlia mosaic caulimovirus (DMV) encodes six open reading frames. Generally, caulimovirus gene VI products (P6s) are thought to be multifunctional proteins required for viral infection and it is likely that self-association is required for some of these functions. In this study, yeast two-hybrid and maltose binding protein (MBP) pull-down assays indicated that full-length DMV P6 specifically self-associates. Further analyses indicated that only the DMV P6 N-terminal region, consisting of 115 amino acids, interacts with full-length P6 and with itself. This distinguishes the DMV P6 from its Cauliflower mosaic virus counterpart, which contains four regions involved in self-association. Thus, our results suggest that each caulimovirus P6 may possess a unique pattern of protein-protein interactions. Bioinformatic tools identified a putative nuclear exclusion signal located between amino acid residues 10-20, suggesting another possible function for the P6 N-terminal region. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. N-Terminal His-Tagged AtTPR7 Interactions with Hsp70 and Hsp90 Proteins

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    ANANDAYU PRADITA

    2014-12-01

    Full Text Available Post-translational protein import into organelles is an important process to maintain cellular functions. During preprotein transport in the cytosol, chaperones, such as heat shock protein 70 (Hsp70 and heat shock protein 90 (Hsp90, are functioning to prevent aggregation and to maintain the correct protein folding of preproteins. This research was conducted in order to understand the chaperone-mediated, post-translational import of preproteins into the endoplasmic reticulum of Arabidopsis thaliana. AtTPR7 (Arabidopsis thaliana Tetratrico Peptide Repeat 7 is found in the endoplasmic reticulum and contains TPR domain, which mediates protein interaction with cytosolic Hsp70 and Hsp90. In this study, recombinant AtTPR7 was expressed in E. coli BL21 (DE3-RIPL cells and purified using an N-terminal His-tag. In order to study the interactions of the protein with the chaperones, we used pulldown and Western blot assays. We could thereby show that the N-terminally His-tagged AtTPR7 protein interacted with Hsp70 and Hsp90.

  13. Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA.

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    Justin Doritchamou

    Full Text Available The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM. It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity- and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development.

  14. Functional characterization of heat-shock protein 90 from Oryza sativa and crystal structure of its N-terminal domain.

    Science.gov (United States)

    Raman, Swetha; Suguna, Kaza

    2015-06-01

    Heat-shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that is essential for the normal functioning of eukaryotic cells. It plays crucial roles in cell signalling, cell-cycle control and in maintaining proteome integrity and protein homeostasis. In plants, Hsp90s are required for normal plant growth and development. Hsp90s are observed to be upregulated in response to various abiotic and biotic stresses and are also involved in immune responses in plants. Although there are several studies elucidating the physiological role of Hsp90s in plants, their molecular mechanism of action is still unclear. In this study, biochemical characterization of an Hsp90 protein from rice (Oryza sativa; OsHsp90) has been performed and the crystal structure of its N-terminal domain (OsHsp90-NTD) was determined. The binding of OsHsp90 to its substrate ATP and the inhibitor 17-AAG was studied by fluorescence spectroscopy. The protein also exhibited a weak ATPase activity. The crystal structure of OsHsp90-NTD was solved in complex with the nonhydrolyzable ATP analogue AMPPCP at 3.1 Å resolution. The domain was crystallized by cross-seeding with crystals of the N-terminal domain of Hsp90 from Dictyostelium discoideum, which shares 70% sequence identity with OsHsp90-NTD. This is the second reported structure of a domain of Hsp90 from a plant source.

  15. Characterization of four new monoclonal antibodies against the distal N-terminal region of PrPc

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    Alessandro Didonna

    2015-03-01

    Full Text Available Prion diseases are a group of fatal neurodegenerative disorders that affect humans and animals. They are characterized by the accumulation in the central nervous system of a pathological form of the host-encoded prion protein (PrPC. The prion protein is a membrane glycoprotein that consists of two domains: a globular, structured C-terminus and an unstructured N-terminus. The N-terminal part of the protein is involved in different functions in both health and disease. In the present work we discuss the production and biochemical characterization of a panel of four monoclonal antibodies (mAbs against the distal N-terminus of PrPC using a well-established methodology based on the immunization of Prnp0/0 mice. Additionally, we show their ability to block prion (PrPSc replication at nanomolar concentrations in a cell culture model of prion infection. These mAbs represent a promising tool for prion diagnostics and for studying the physiological role of the N-terminal domain of PrPC.

  16. Depletion of the human N-terminal acetyltransferase hNaa30 disrupts Golgi integrity and ARFRP1 localization.

    Science.gov (United States)

    Starheim, Kristian K; Kalvik, Thomas V; Bjørkøy, Geir; Arnesen, Thomas

    2017-04-30

    The organization of the Golgi apparatus (GA) is tightly regulated. Golgi stack scattering is observed in cellular processes such as apoptosis and mitosis, and has also been associated with disruption of cellular lipid metabolism and neurodegenerative diseases. Our studies show that depletion of the human N-α-acetyltransferase 30 (hNaa30) induces fragmentation of the Golgi stack in HeLa and CAL-62 cell lines. The GA associated GTPase ADP ribosylation factor related protein 1 (ARFRP1) was previously shown to require N-terminal acetylation for membrane association and based on its N-terminal sequence, it is likely to be a substrate of hNaa30. ARFRP1 is involved in endosome-to- trans -Golgi network (TGN) traffic. We observed that ARFRP1 shifted from a predominantly cis -Golgi and TGN localization to localizing both Golgi and non-Golgi vesicular structures in hNaa30-depleted cells. However, we did not observe loss of membrane association of ARFRP1. We conclude that hNaa30 depletion induces Golgi scattering and induces aberrant ARFRP1 Golgi localization. © 2017 The Author(s).

  17. Neurospora tryptophan synthase: N-terminal analysis and the sequence of the pyridoxal phosphate active site peptide

    International Nuclear Information System (INIS)

    Pratt, M.L.; Hsu, P.Y.; DeMoss, J.A.

    1986-01-01

    Tryptophan synthase (TS), which catalyzes the final step of tryptophan biosynthesis, is a multifunctional protein requiring pyridoxal phosphate (B6P) for two of its three distinct enzyme activities. TS from Neurospora has a blocked N-terminal, is a homodimer of 150 KDa and binds one mole of B6P per mole of subunit. The authors shown the N-terminal residue to be acyl-serine. The B6P-active site of holoenzyme was labelled by reduction of the B6P-Schiff base with [ 3 H]-NaBH 4 , and resulted in a proportionate loss of activity in the two B6P-requiring reactions. SDS-polyacrylamide gel electrophoresis of CNBr-generated peptides showed the labelled, active site peptide to be 6 KDa. The sequence of this peptide, purified to apparent homogeneity by a combination of C-18 reversed phase and TSK gel filtration HPLC is: gly-arg-pro-gly-gln-leu-his-lys-ala-glu-arg-leu-thr-glu-tyr-ala-gly-gly-ala-gln-ile-xxx-leu-lys-arg-glu-asp-leu-asn-his-xxx-gly-xxx-his-/sub ***/-ile-asn-asn-ala-leu. Although four residues (xxx, /sub ***/) are unidentified, this peptide is minimally 78% homologous with the corresponding peptide from yeast TS, in which residue (/sub ***/) is the lysine that binds B6P

  18. The N-terminal pro region mediates retention of unprocessed type-I PME in the Golgi apparatus.

    Science.gov (United States)

    Wolf, Sebastian; Rausch, Thomas; Greiner, Steffen

    2009-05-01

    The pectin matrix of the cell wall, a complex and dynamic network, impacts on cell growth, cell shape and signaling processes. A hallmark of pectin structure is the methylesterification status of its major component, homogalacturonan (HGA), which affects the biophysical properties and enzymatic turnover of pectin. The pectin methylesterases (PMEs), responsible for de-esterification, encompass a protein family of more than 60 isoforms in the Arabidopsis genome. The pivotal role of PME in the regulation of pectin properties also requires tight control at the post-translational level. Type-I PMEs are characterized by an N-terminal pro region, which exhibits homology with pectin methylesterase inhibitors (PMEIs). Here, we demonstrate that the proteolytic removal of the N-terminal pro region depends on conserved basic tetrad motifs, occurs in the early secretory pathway, and is required for the subsequent export of the PME core domain to the cell wall. In addition, we demonstrate the involvement of AtS1P, a subtilisin-like protease, in Arabidopsis PME processing. Our results indicate that the pro region operates as an effective retention mechanism, keeping unprocessed PME in the Golgi apparatus. Consequently, pro-protein processing could constitute a post-translational mechanism regulating PME activity.

  19. Prevalence of Exercise-Induced Bronchospasm by laboratory exercise challenge among Ragunan Sport School athletes

    Directory of Open Access Journals (Sweden)

    Ignatio Rika

    2008-03-01

    Full Text Available Exercise-induced bronchospasm (EIB is a common condition among adolescent athletes. There has been no study examining the prevalence of EIB among adolescent athletes in Indonesia. This study aimed to get the prevalence of EIB among Ragunan Sport School athletes by laboratory exercise challenge. Subjects performed static cycle ergometer exercise (Monark, Sweden to reach minimal workload of 90% maximal heart rate. Force expiratory ventilation (FEV₁ was examined by spirometry (Minato AS-PAL, Japan at minute 0, 5, 10 and 20 post exercise. The EIB was defined as a decline of FEV₁ as much as 10% or more from baseline value. Room temperature and humidity were 28°C-31°C and 74%-82% respectively. There were 168 athletes from 12 sport types who participated in this study. Among them, 23 athletes (13.7% were EIB positive. The highest percentage of EIB was in taekwondo (54.5%. Sixteen athletes with EIB (70% were from less asthmogenic sports. Athletes with EIB consisted of 17 (17.5% females and 6 (8.4% males. In conclusion, the prevalence of EIB among adolescent athletes was moderately high, and was more prevalent in female. More over, laboratory exercise challenge could elicit EIB in less asthmogenic sport. (Med J Indones 2008; 17: 33-6Keywords: adolescent athlete, asthmogenic sports

  20. [Detection of exercise-induced bronchospasm in sixth-grade students: impact of health education].

    Science.gov (United States)

    Charton, C; Droulers, I; Girault, E; Laurent, C; Housset, B; Delacourt, C

    2002-03-01

    Underdiagnosis of asthma is frequent in children and may be improved by the development of school-based health programs. We developed an educational program in 11-year-old schoolchildren who participated in a screening test for exercise-induced asthma (EIA). All children were given an asthma questionnaire before and after two educational sessions. Mean score for asthma knowledge quiz increased from 63 to 85% (p children (3.7%) were initially considered as asthmatic and showed better responses than non-asthmatic children. Peak expiratory flow (PEF) was measured before and after an outside running exercise. A fall in PEF of at least 15% was considered an abnormal result. Seventy-height children (8%) had a decrease in PEF, including 65 children initially not recognized as asthmatic. For these latter, a medical evaluation was recommended to parents. Only 28 of these children gave informations on follow-up: 19 had lung function tests, two received a treatment without preliminary function test, and seven had neither lung function test nor treatment. Among the children who realized lung function tests, five had criteria for airway obstruction at baseline, and ten had significant bronchial hyperreactivity. However, a new screening test revealed that only a small minority of children initially not recognized as asthmatic but having decreased their PEF, were consequently considered as asthmatic by their practitioner, even in case of positive lung function test.