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Sample records for serum b-type natriuretic

  1. Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography

    PubMed Central

    Gan, Lu; Feng, Cong; Liu, Chunlei; Tian, Shuping; Song, Xiang; Yang, Li

    2016-01-01

    The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47–82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA. PMID:27446259

  2. Endothelial actions of atrial and B-type natriuretic peptides

    PubMed Central

    Kuhn, Michaela

    2012-01-01

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

  3. Endothelial actions of atrial and B-type natriuretic peptides.

    PubMed

    Kuhn, Michaela

    2012-05-01

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

  4. B-type natriuretic peptides and mortality after stroke

    PubMed Central

    García-Berrocoso, Teresa; Giralt, Dolors; Bustamante, Alejandro; Etgen, Thorleif; Jensen, Jesper K.; Sharma, Jagdish C.; Shibazaki, Kensaku; Saritas, Ayhan; Chen, Xingyong; Whiteley, William N.

    2013-01-01

    Objective: To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information. Methods: Suitable studies for meta-analysis were found by searching MEDLINE and EMBASE databases until October 26, 2012. Weighted mean differences measured effect size; meta-regression and publication bias were assessed. Individual participant data were used to estimate effects by logistic regression and to evaluate BNP/NT-proBNP additional predictive value by area under the receiver operating characteristic curves, and integrated discrimination improvement and categorical net reclassification improvement indexes. Results: Literature-based meta-analysis included 3,498 stroke patients from 16 studies and revealed that BNP/NT-proBNP levels were 255.78 pg/mL (95% confidence interval [CI] 105.10–406.47, p = 0.001) higher in patients who died; publication bias entailed the loss of this association. Individual participant data analysis comprised 2,258 stroke patients. After normalization of the data, patients in the highest quartile had double the risk of death after adjustment for clinical variables (NIH Stroke Scale score, age, sex) (odds ratio 2.30, 95% CI 1.32–4.01 for BNP; and odds ratio 2.63, 95% CI 1.75–3.94 for NT-proBNP). Only NT-proBNP showed a slight added value to clinical prognostic variables, increasing discrimination by 0.028 points (integrated discrimination improvement index; p < 0.001) and reclassifying 8.1% of patients into correct risk mortality categories (net reclassification improvement index; p = 0.003). Neither etiology nor time from onset to death affected the association of BNP/NT-proBNP with mortality. Conclusion: BNPs are associated with poststroke mortality independent of NIH Stroke Scale score, age, and sex. However, their translation to clinical practice seems difficult because BNP

  5. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  6. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  7. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  8. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  9. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  10. B-type natriuretic peptide rapid assay: a diagnostic test for heart failure.

    PubMed

    Ancheta, Irma B

    2006-01-01

    Hospitals are constantly besieged with congestive heart failure admissions. Current studies show that the advent of the B-type natriuretic peptide (BNP) rapid assay as a quick and easy blood test is beneficial to nurses in confirming the diagnosis of heart failure. B-type natriuretic peptide is a neurohormone produced by the failing heart in response to increased volume and cardiac overload. The BNP rapid assay measures the presence of BNP levels present in the circulating bloodstream to confirm the diagnosis of congestive heart failure. It is a simple blood test that can be done at the bedside or at the clinic so it is a valid point-of-care modality. Elevated levels suggest severity of heart failure and possibility of sudden death. This article focuses on the description of the diagnostic performance of the BNP rapid assay, its clinical dimensions, and its implications to nursing practice and collaborative practice models.

  11. B-type natriuretic peptide level in a patient with constrictive pericarditis.

    PubMed

    Brown, Todd; Hollman, Jay

    2006-12-01

    We report the case of a 35-year-old man with constrictive pericarditis who had a B-type natriuretic peptide (BNP) level of 129 pg/dl despite a left ventricular end diastolic pressure of 35 mmHg. We discuss a possible explanation for the relatively low BNP level given this patient's markedly elevated intracavitary pressures in the setting of constrictive pericarditis.

  12. B-type natriuretic peptide and heart failure: what can we learn from clinical trials?

    PubMed

    Binoun-A-Egom, Christian; Andreas, Angelo; Klimas, Jan; Valentova, Vanda; Kruzliak, Peter; Egom, Emmanuel E

    2015-05-13

    The B-type natriuretic peptide (BNP), may favor natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient who had poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these has resulted in a better outcome. The current challenge for BNP research in acute HF lies in a failure of concept and reluctance to abandon a demonstrably ineffectual research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP as well as a better integration of basic and clinical science. This article is protected by copyright. All rights reserved.

  13. The use of B-type natriuretic peptide to diagnose congestive heart failure.

    PubMed

    Gray, Jeffery R

    2006-01-01

    This paper explains the background and current use of B-type natriuretic peptide (BNP) assays to differentiate congestive heart failure (CHF) from other causes of dyspnea. With a large and growing elderly population, CHF is being diagnosed much more often in emergency rooms in the United States. Doctors need a way to quickly distinguish whether a patient with respiratory distress is suffering from cardiac insufficiency or another etiology. BNP is released from the ventricles in response cardiac overload from CHF or some other form of left ventricular systolic dysfunction. Therefore, the detection and measurement of BNP is a fast and accurate method of determining if CHF is the cause of a patient's breathing difficulties.

  14. B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide in pediatric patients with pulmonary arterial hypertension

    PubMed Central

    Takatsuki, Shinichi; Wagner, Brandie D; Ivy, David Dunbar

    2011-01-01

    Objectives B-type natriuretic peptide (BNP) and the amino-terminal fragment (NTproBNP) correlate with clinical variables, but have not been simultaneously studied in a large number of pediatric patients with pulmonary arterial hypertension (PAH). The purpose of our investigation was to compare BNP and NTproBNP with clinical indicators of disease in a pediatric PAH population for which biomarkers are much needed. Design We retrospectively compared BNP and NTproBNP levels with exercise capacity, echocardiographic data, and hemodynamics in PAH patients under 21 years-old. Two hundred sixty three blood samples from 88 pediatric PAH patients were obtained, with BNP and NTproBNP drawn at the same time. Results There was a correlation between BNP and NTproBNP with mean pulmonary arterial pressure/mean arterial pressure (mPAP/mSAP) ratio (r=0.40 p<0.01, r=0.45 p<0.01, respectively), mean right atrial pressure (mRAP) (r=0.48 p<0.01, r=0.48 p<0.01), and tricuspid regurgitant (TR) velocity (r=0.36 p<0.01, r=0.41 p<0.01). BNP and NTproBNP are associated with 6 minute walking distance, mPAP, mPAP/mSAP ratio, mRAP, pulmonary vascular resistance index (PVRI), and TR velocity when investigated longitudinally. On the average, a 1 unit increase in log BNP or NTproBNP was associated with 4.5 unitsxm2 or 3.4 unitsxm2 increase in PVRI, respectively. There was a strong correlation between log BNP and log NTproBNP measurements (r= 0.87, p<0.01). Conclusion In pediatric PAH, BNP and NTProBNP are strongly correlated and predict changes in clinical variables and hemodynamics. In a cross-sectional analysis, NTproBNP correlated with echocardiographic and exercise data better than BNP; NTproBNP showed less within patient variability over time, therefore NTproBNP can add additional information towards predicting these clinical measurements. PMID:22325151

  15. The cyclic guanosine monophosphate/B-type natriuretic peptide ratio and mortality in advanced heart failure

    PubMed Central

    Lourenço, Patrícia; Araújo, José Paulo; Azevedo, Ana; Ferreira, António; Bettencourt, Paulo

    2009-01-01

    Aims Attenuation of the effects of natriuretic peptides has been demonstrated in animal models but studies in humans are scarce, particularly concerning renal attenuation. We investigated the attenuation of B-type natriuretic peptide (BNP) in chronic advanced heart failure (HF). Methods and results We included 62 outpatients with HF and severe left ventricular systolic dysfunction. Cases had at least one hospital admission or emergency department visit for acute HF in the previous year and were in NYHA class III/IV despite optimized therapy. The individual age- and sex-matched controls were symptomatically controlled (NYHA I and II). We collected 24 h urine and a blood sample from all patients. Plasma BNP and plasma (pcGMP) and urine cyclic guanosine monophosphate (ucGMP) were measured. Patients were followed for 3 months for hospital admission or all-cause death. ucGMP to plasma BNP (ucGMP/BNP) ratio was attenuated in cases vs. controls [median (IQR): 8354 (4293–16 456) vs. 12 693 (6896–22 851)]. There were no differences in pcGMP to BNP (pcGMP/BNP) ratio or urine cGMP excretion. Patients with worse outcome had lower pcGMP/BNP [260 (86–344) vs. 381 (244–728) in patients without adverse outcome events] and lower ucGMP/BNP [4146 (2207–9363) vs. 10 922 (7495–19 971)]. Conclusion Renal NP’s second messenger production is attenuated in advanced HF. Patients with worse outcome have lower ucGMP/BNP and pcGMP/BNP ratios. PMID:19168517

  16. Arterial Remodeling in B-Type Natriuretic Peptide Knock-Out Females

    PubMed Central

    Holditch, Sara J.; Schreiber, Claire A.; Burnett, John C.; Ikeda, Yasuhiro

    2016-01-01

    Sexual dimorphisms are recognized in cardiovascular conditions such as hypertension, stroke, thrombosis and vasculitis. B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. The anti-hypertensive, vasodilatory, anti-fibrotic, and anti-hypertrophic properties of BNP are well established in male animal models. Although circulating BNP levels are higher in women, when compared to age-matched men, the cardiovascular protective propensity of BNP in females is poorly understood. We assessed the cardiovascular consequences of BNP deletion in genetically null (Nppb−/−) female rat lines. Throughout the study, blood pressure (BP) remained uninfluenced by genotype, and cardiorenal consequences of BNP knock out remained minor. Unexpectedly, approximately 60% of Nppb−/− females developed mesenteric polyarteritis-nodosa (PAN)-like vasculitis in their life span, some as early as 4 months of age. Mesenteric lesions involved intense arterial remodeling, progressive inflammation, occluded lumens, and less frequently intestinal necrosis and multiple visceral arterial aneurysms. Cumulative pathologies resulted in a significant decline in survival of the Nppb−/− female. This study highlights BNP’s vasoprotective propensity, bringing to light a possible sex specific difference in the cardiovascular protection provided by BNP. Defects in the BNP/GC-A/cGMP pathway may play a role in arteriopathies in women, while GC-A agonists may provide effective therapy for arteritis. PMID:27162120

  17. B-Type Natriuretic Peptide Levels Predict Ventricular Arrhythmia Post Left Ventricular Assist Device Implantation.

    PubMed

    Hellman, Yaron; Malik, Adnan S; Lin, Hongbo; Shen, Changyu; Wang, I-Wen; Wozniak, Thomas C; Hashmi, Zubair A; Pickrell, Jeanette; Jani, Milena; Caccamo, Marco A; Gradus-Pizlo, Irmina; Hadi, Azam

    2015-12-01

    B-type natriuretic peptide (BNP) levels have been shown to predict ventricular arrhythmia (VA) and sudden death in patients with heart failure. We sought to determine whether BNP levels before left ventricular assist device (LVAD) implantation can predict VA post LVAD implantation in advanced heart failure patients. We conducted a retrospective study consisting of patients who underwent LVAD implantation in our institution during the period of May 2009-March 2013. The study was limited to patients receiving a HeartMate II or HeartWare LVAD. Acute myocardial infarction patients were excluded. We compared between the patients who developed VA within 15 days post LVAD implantation to the patients without VA. A total of 85 patients underwent LVAD implantation during the study period. Eleven patients were excluded (five acute MI, four without BNP measurements, and two discharged earlier than 13 days post LVAD implantation). The incidence of VA was 31%, with 91% ventricular tachycardia (VT) and 9% ventricular fibrillation. BNP remained the single most powerful predictor of VA even after adjustment for other borderline significant factors in a multivariate logistic regression model (P < 0.05). BNP levels are a strong predictor of VA post LVAD implantation, surpassing previously described risk factors such as age and VT in the past.

  18. Cortical Brain Connectivity and B-Type Natriuretic Peptide in Patients With Congestive Heart Failure.

    PubMed

    Vecchio, Fabrizio; Miraglia, Francesca; Valeriani, Lavinia; Scarpellini, Maria Gabriella; Bramanti, Placido; Mecarelli, Oriano; Rossini, Paolo M

    2015-07-01

    The brain has a high level of complexity and needs continuous oxygen supply. So it is clear that any pathological condition, or physiological (aging) change, in the cardiovascular system affects functioning of the central nervous system. We evaluated linear aspects of the relationship between the slowness of cortical rhythms, as revealed by the modulation of a graph connectivity parameter, and congestive heart failure (CHF), as a reflection of neurodegenerative processes. Eyes-closed resting electroencephalographic (EEG) data of 10 patients with CHF were recorded by 19 electrodes positioned according the international 10-20 system. Graph theory function (normalized characteristic path length λ) was applied to the undirected and weighted networks obtained by lagged linear coherence evaluated by eLORETA software, therefore getting rid of volumetric propagation influences. The EEG frequency bands of interest were: delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). The analysis between B-type natriuretic peptide (BNP) values and λ showed positive correlation in delta, associated with a negative correlation in alpha 2 band. Namely, the higher the severity of the disease (as revealed by the BNP vales), the higher the λ in delta, and lower in alpha 2 band. Results suggest that delta and alpha λ indices are good markers of the severity of CHF.

  19. B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.

    PubMed

    Vila, Greisa; Grimm, Gabriele; Resl, Michael; Heinisch, Birgit; Einwallner, Elisa; Esterbauer, Harald; Dieplinger, Benjamin; Mueller, Thomas; Luger, Anton; Clodi, Martin

    2012-10-01

    Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

  20. Bioimpedance analysis and plasma B-type natriuretic peptide assay may cooperate in diagnosing and managing heart failure.

    PubMed

    Tamagno, Gianluca; Guzzon, Samuele

    2006-06-01

    We describe the case of an obese patient presenting leg oedema, progressive oliguria, orthopnoea and mild increased B-type natriuretic peptide (BNP) levels. Bioimpedance analysis (BIA) provided additional data for the interpretation of the plasma BNP values, contributing to the diagnosis of heart failure and the appropriate management of the patient. In our mind, BIA could represent a useful tool for integrating the plasma BNP assay in both diagnosis and management of heart failure.

  1. State of the art of immunoassay methods for B-type natriuretic peptides: An update.

    PubMed

    Clerico, Aldo; Franzini, Maria; Masotti, Silvia; Prontera, Concetta; Passino, Claudio

    2015-01-01

    The aim of this review article is to give an update on the state of the art of the immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides. Using chromatographic procedures, several studies reported an increasing number of circulating peptides related to BNP in human plasma of patients with heart failure. These peptides may have reduced or even no biological activity. Furthermore, other studies have suggested that, using immunoassays that are considered specific for BNP, the precursor of the peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of patients with heart failure. Because BNP immunoassay methods show large (up to 50%) systematic differences in values, the use of identical decision values for all immunoassay methods, as suggested by the most recent international guidelines, seems unreasonable. Since proBNP significantly cross-reacts with all commercial immunoassay methods considered specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians should take into account that there are large systematic differences between methods when they compare results from different laboratories that use different BNP immunoassays. On the other hand, clinical laboratories should take part in external quality assessment (EQA) programs to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors believe that the development of more specific methods for the active peptide, BNP1-32, should reduce the systematic differences between methods and result in better harmonization of results.

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

    PubMed

    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

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

    PubMed

    Torres-Courchoud, I; Chen, H H

    2016-10-01

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

  4. B-type natriuretic peptide and adiponectin releases in rat model of myocardial damage induced by isoproterenol administration

    PubMed Central

    Hasić, Sabaheta; Hadžović-Džuvo, Almira; Jadrić, Radivoj; Kiseljaković, Emina

    2013-01-01

    B-type natriuretic peptide (BNP) and adiponectin play important role in the cardiovascular homeostasis regulation. We investigated BNP and adiponectin serum levels followed by isoproterenol (ISO) administration to rats and explored the relationship between them. Cardiac troponin I (cTnI) blood level was used as biochemical evidence of myocardial damage development. Adult male Wistar rats (average body weight 273.33±21.63 g) were distributed into groups: control group received saline (n=6) and ISO groups (n=12) treated with ISO (subcutaneous single dose 100 mg/kg of rat body weight). ISO group was divided into two groups according to the time of BNP, adiponectin and cTnI determination: ISO I (n=6; 2 hours after ISO administration); ISO II (n=6; 4 hours after ISO administration). Blood for determination of parameters was taken from rat abdominal aorta. BNP, adiponectin and cTnI were determined by ELISA method. Data were statistically analysed by using SPSS version13 computer program. P value less 0.05 was considered statistically significant. Blood BNP and adiponectin were lower at 2 hours after ISO administration in comparison with control group (p=0.004 for BNP and p=0.174 for adiponectin). Four hours after ISO administration, we have noted significant elevation of both parameters compared to ISO I group (p=0.004 for BNP;p=0.02 for adiponectin). Test of correlation have showed significant relation between their blood levels during experimental period (rho=0.577; p=0.01). BNP and adiponectin are not simple indicators of myocardial damage development. They have possible associated and additive effects in cardiovascular homeostasis regulation. PMID:24289757

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

    PubMed

    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

  6. Plasma atrial natriuretic peptide and N-terminal pro B-type natriuretic peptide concentrations in dogs with right-sided congestive heart failure

    PubMed Central

    KANNO, Nobuyuki; HORI, Yasutomo; HIDAKA, Yuichi; CHIKAZAWA, Seishiro; KANAI, Kazutaka; HOSHI, Fumio; ITOH, Naoyuki

    2015-01-01

    The clinical utility of plasma natriuretic peptide concentrations in dogs with right-sided congestive heart failure (CHF) remains unclear. We investigated whether plasma levels of atrial natriuretic peptide (ANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are useful for assessing the congestive signs of right-sided heart failure in dogs. This retrospective study enrolled 16 healthy dogs and 51 untreated dogs with presence (n=28) or absence (n=23) of right-sided CHF. Medical records of physical examinations, thoracic radiography and echocardiography were reviewed. The plasma concentration of canine ANP was measured with a chemiluminescent enzyme immunoassay. Plasma NT-proBNP concentrations were determined using an enzyme immunoassay. Plasma ANP and NT-proBNP concentrations in dogs with right-sided CHF were significantly higher than in healthy controls and those without right-sided CHF. The plasma NT-proBNP concentration >3,003 pmol/l used to identify right-sided CHF had a sensitivity of 88.5% and specificity of 90.3%. An area under the ROC curve (AUC) was 0.93. The AUC for NT-proBNP was significantly higher than the AUCs for the cardiothoracic ratio, vertebral heart score, ratio of right ventricular end-diastolic internal diameter to body surface area, tricuspid late diastolic flow and ratio of the velocities of tricuspid early to late diastolic flow. These results suggest that plasma ANP and NT-proBNP concentrations increase markedly in dogs with right-sided CHF. Particularly, NT-proBNP is simple and helpful biomarkers to assess the right-sided CHF. PMID:26607133

  7. Predictors of Left Ventricle Remodeling: Combined Plasma B-type Natriuretic Peptide Decreasing Ratio and Peak Creatine Kinase-MB.

    PubMed

    Hsu, Jen-Te; Chung, Chang-Min; Chu, Chi-Ming; Lin, Yu-Shen; Pan, Kuo-Li; Chang, Jung-Jung; Wang, Po-Chang; Chang, Shih-Tai; Yang, Teng-Yao; Jang, Shih-Jung; Yang, Tsung-Han; Hsiao, Ju-Feng

    2017-01-01

    Background: Previous studies reported that patients who had an acute myocardial infarction (AMI) have found that measuring B-type natriuretic peptide (BNP) during the subacute phase of left ventricular (LV) remodeling can predict the possible course of LV remodeling. This study assessed the use of serial BNP serum levels combined with early creatine kinase-MB (CK-MB) to predict the development of significant LV remodeling in AMI patients. Methods: Nighty-seven patients with new onset AMI were assessed using serial echocardiographic studies and serial measurements of BNP levels, both performed on day-2 (BNP1), day-7 (BNP2), day-90 (BNP3), and day-180 (BNP4) after admission. LV remodeling was defined as >20% increase in biplane LV end-diastolic volume on day-180 compared to baseline (day-2). Results: Patients were divided into LV remodeling [LVR(+)] and non LV remodeling [LVR(-)] groups. No first-week BNP level was found to predict remodeling. However, the two groups had significantly different day-90 BNP level (208.1 ± 263.7 pg/ml vs. 82.4 ± 153.7 pg/ml, P = 0.039) and significantly different 3-month BNP decrease ratios ( R BNP13) (14.4 ± 92.2% vs. 69.4 ± 25.9%, P < 0.001). The appropriate cut-off value for R BNP13 was 53.2% (AUC = 0.764, P < 0.001). Early peak CK-MB (cut-off 48.2 ng/ml; AUC = 0.672; P = 0.014) was another independent predictor of remodeling. Additionally, combining peak CK-MB and R BNP13 offered an excellent discrimination for half-year remodeling when assessed by ROC curve (AUC = 0.818, P < 0.001). Conclusion: R BNP13 is a significant independent predictor of 6-month LV remodeling. The early peak CK-MB additionally offered an incremental power to the predictions derived from serial BNP examinations.

  8. Predictors of Left Ventricle Remodeling: Combined Plasma B-type Natriuretic Peptide Decreasing Ratio and Peak Creatine Kinase-MB

    PubMed Central

    Hsu, Jen-Te; Chung, Chang-Min; Chu, Chi-Ming; Lin, Yu-Shen; Pan, Kuo-Li; Chang, Jung-Jung; Wang, Po-Chang; Chang, Shih-Tai; Yang, Teng-Yao; Jang, Shih-Jung; Yang, Tsung-Han; Hsiao, Ju-Feng

    2017-01-01

    Background: Previous studies reported that patients who had an acute myocardial infarction (AMI) have found that measuring B-type natriuretic peptide (BNP) during the subacute phase of left ventricular (LV) remodeling can predict the possible course of LV remodeling. This study assessed the use of serial BNP serum levels combined with early creatine kinase-MB (CK-MB) to predict the development of significant LV remodeling in AMI patients. Methods: Nighty-seven patients with new onset AMI were assessed using serial echocardiographic studies and serial measurements of BNP levels, both performed on day-2 (BNP1), day-7 (BNP2), day-90 (BNP3), and day-180 (BNP4) after admission. LV remodeling was defined as >20% increase in biplane LV end-diastolic volume on day-180 compared to baseline (day-2). Results: Patients were divided into LV remodeling [LVR(+)] and non LV remodeling [LVR(-)] groups. No first-week BNP level was found to predict remodeling. However, the two groups had significantly different day-90 BNP level (208.1 ± 263.7 pg/ml vs. 82.4 ± 153.7 pg/ml, P = 0.039) and significantly different 3-month BNP decrease ratios (RBNP13) (14.4 ± 92.2% vs. 69.4 ± 25.9%, P < 0.001). The appropriate cut-off value for RBNP13 was 53.2% (AUC = 0.764, P < 0.001). Early peak CK-MB (cut-off 48.2 ng/ml; AUC = 0.672; P = 0.014) was another independent predictor of remodeling. Additionally, combining peak CK-MB and RBNP13 offered an excellent discrimination for half-year remodeling when assessed by ROC curve (AUC = 0.818, P < 0.001). Conclusion: RBNP13 is a significant independent predictor of 6-month LV remodeling. The early peak CK-MB additionally offered an incremental power to the predictions derived from serial BNP examinations. PMID:28138312

  9. Assessing cardiovascular risk in children with chronic kidney disease. B-type natriuretic peptide: a potential new marker.

    PubMed

    Ariceta, Gema; Brooks, Ellen R; Langman, Craig B

    2005-12-01

    Elevated plasma B-type natriuretic peptide (BNP) level is a hallmark of altered left ventricular (LV) structure and function. Measurement of circulating BNP has proved to be a sensitive and specific diagnostic test for congestive heart failure (CHF) and coronary syndrome in adults. Further, BNP levels constitute a strong predictive marker for future cardiovascular (CV) events. In high CV risk populations, such as adults with hypertension or chronic kidney disease (CKD), increased BNP predicts CV morbidity and mortality in symptomatic or asymptomatic patients. However, caution is needed in interpreting plasma BNP levels, as they increase with both age and decreased renal function. Despite increasing evidence of the value of BNP in the medical literature in adults, data in children are limited to those with congenital heart disease. It is appropriate to analyze the potential application of this tool in children with CKD, a well-known factor for CV disease.

  10. B-type Natriuretic Peptide Assay in Differentiating Congestive Heart Failure from Lung Disease in Patients Presenting with Dyspnea.

    PubMed

    Islam, M A; Bari, M S; Islam, M N; Bari, M A; Siddique, S R; Islam, M Z; Begum, M S; Ahammed, S U; Rahman, M A

    2016-07-01

    This cross-sectional analytical study was conducted in Cardiology & Medicine Department of Mymensingh Medical College Hospital. After fulfilling the exclusion & inclusion criteria, B-type natriuretic peptide concentrations were measured in a convenience sample of 100 predominantly male (94%) dyspnic patients who got admitted in Cardiology & Medicine Department of Mymensingh Medical College & Hospital from November 2013 to October 2014. The diagnosis of Congestive Heart Failure (CHF) was based on generally accepted Framingham criteria with corroborative information including hospital course (response to diuretics, vasodilators, inotropes or hemodynamic monitoring) and results of further cardiac testing, including echocardiography. Patients with right heart failure from cor pulmonale were classified as having CHF. Pulmonary disease was confirmed by using the following diagnostic tools: i) A chest X-ray without signs of heart enlargement or pulmonary venous hypertension or a chest X-ray with signs of chronic obstructive lung disease, ii) Normal heart function as seen by echocardiography, iii) Abnormal pulmonary function tests or follow-up results and iv) A positive response to treatment with steroids, nebulizers or antibiotics in hospital. Patients with CHF (n=50) had mean BNP level 1146.72pg/ml (range 103 to 5000pg/ml), which is significantly higher than the group of patients with a final diagnosis of pulmonary disease (n=50) whose BNP was 34pg/ml (range 10 to 90pg/ml) (p<0.05). In conclusion, it was found that B-type natriuretic peptide is an important biomarker for differentiating congestive heart failure from lung disease in patients presenting with dyspnea.

  11. B-type natriuretic peptide-guided therapy and length of hospital stay post left ventricular assist device implantation.

    PubMed

    Hellman, Yaron; Malik, Adnan S; Lin, Hongbo; Shen, Changyu; Wang, I-Wen; Wozniak, Thomas C; Hashmi, Zubair A; Shaukat, Arslan; Pickrell, Jeanette; Caccamo, Marco A; Gradus-Pizlo, Irmina; Hadi, Azam

    2015-01-01

    B-type natriuretic peptide (BNP)-guided therapy during the early postoperative period following left ventricular assist device (LVAD) implantation has not been well described in the literature. We conducted a retrospective cohort study consisting of consecutive patients who underwent LVAD implantation at our institution during May 2009 to March 2013. The study was limited to patients receiving HeartMate II (Thoratec) or HVAD (HeartWare) LVADs. Patients with acute myocardial infarction were excluded. We compared between patients with multiple postoperative BNP tests (BNP-guided therapy) and earlier period patients who typically had only a baseline BNP measurement (non-BNP-guided therapy). A total of 85 patients underwent LVAD implantation during the study period. Eight patients were excluded (five acute myocardial infarction, three without BNP measurements). The only differences in the baseline characteristics of BNP versus non-BNP-guided therapy included age and female gender. The postoperative length of hospital stay (LOS) in the BNP-guided therapy group was 5 days shorter when compared with the non-BNP-guided therapy group. In multivariate analysis, BNP-guided therapy remained a significant predictor of reduced LOS. The use of repeated BNP measurements during the early postoperative period was associated with a significantly lower LOS post LVAD implantation.

  12. Multiplex detection of B-type natriuretic peptide, cardiac troponin I and C-reactive protein with photonic suspension array.

    PubMed

    Lu, Wenbin; Fu, Cong; Chen, Yong; Lu, Jun; Yao, Yuyu; Shen, Chengxing; Gu, Zhongze

    2012-01-01

    A novel photonic suspension array has been developed for multiplex immunoassay. The carriers of this array were silica colloidal crystal beads (SCCBs). The codes of these carriers have characteristic reflection peaks originating from their structural periodicity; therefore they do not suffer from fading, bleaching, quenching or chemical instability. In addition, the fluorescence background of SCCBs is negligible because no fluorescence materials or dyes are involved. With a sandwich method, the proposed suspension array was used for simultaneous multiplex detection of heart failure (HF) and coronary heart disease (CAD) biomarkers in one test tube. The results showed that the three biomarkers: cardiac troponin I (cTnI), C-reactive protein (CRP) and B-type natriuretic peptide (BNP) could be assayed in the ranges of 0.1-500 ng/ml, 1-500 mg/L and 0.02-50 ng/ml with detection limits of 0.01 ng/ml, 0.36 mg/L and 0.004 ng/ml at 3σ, respectively. There were no significant differences between the photonic suspension array and traditional parallel single-analyte test. This novel method demonstrated acceptable accuracy, high detection sensitivity and reproducibility and excellent storage stability. This technique provides a new strategy for low cost, automated, and simultaneous multiplex immunoassays of bio-markers.

  13. Myopericarditis with predominantly right ventricular involvement with normal B-type natriuretic peptide and cardiac tamponade as the initial manifestation of systemic lupus erythematosus.

    PubMed

    Manautou, Luis; Jerjes-Sanchez, Carlos; Meraz, Manuel; Perez-Garcia, Luis F; Diaz-Cid, Antonio; de la Peña-Almaguer, Erasmo; Avila, Cesar; Sanchez, Luis

    2014-08-01

    A previously healthy young man presented with a 12-hour history of sudden dyspnea and severe chest pain at rest. Initial findings of physical examination, electrocardiogram and chest radiography showed typical pericarditis and clinical instability. Echocardiogram revealed small pericardial effusion with right ventricle dilatation. The patient was admitted in the ICU; a new echocardiogram revealed moderate pericardial effusion and diagnosis of pericarditis complicated with acute cardiac tamponade was established. The patient transiently improved after pericardial window. In the following hours, the diagnosis of myocarditis with predominantly right ventricular involvement (MPRVI) with severe right heart failure was supported by clinical, chest radiography and echocardiogram data, despite normal B-type natriuretic peptide. On day 2, cardiac troponin I detection was observed. By day 3, B-type natriuretic peptide in the range of ventricular dysfunction was identified. Cardiovascular magnetic resonance findings supported the diagnosis of MPRVI. A systematic MEDLINE/PubMed from 1993 to 2013 does not identify any cases of MPRVI related to systemic lupus erythematosus. Simultaneous acute MPRVI with normal B-type natriuretic peptide and acute cardiac tamponade heralding the diagnosis of systemic lupus erythematosus, to the best of our knowledge, has not been previously described.

  14. The prognostic value of N-terminal proB-type natriuretic peptide in patients with acute respiratory distress syndrome

    PubMed Central

    Lai, Chih-Cheng; Sung, Mei-I.; Ho, Chung-Han; Liu, Hsiao-Hua; Chen, Chin-Ming; Chiang, Shyh-Ren; Chao, Chien-Ming; Liu, Wei-Lun; Hsing, Shu-Chen; Cheng, Kuo-Chen

    2017-01-01

    We investigated whether N-terminal proB-type natriuretic peptide (NT-proBNP) predicts the prognosis of patients with acute respiratory distress syndrome (ARDS). Between December 1, 2012, and May 31, 2015, this observational study recruited patients admitted to our tertiary medical center who met the Berlin criteria for ARDS and who had their NT-proBNP measured. The main outcome was 28-day mortality. We enrolled 61 patients who met the Berlin criteria for ARDS: 7 were classified as mild, 29 as moderate, and 25 as severe. The median APACHE II scores were 23 (interquartile range [IQR], 18–28), and SOFA scores were 11 (IQR, 8–13). The median lung injury score was 3.0 (IQR, 2.50–3.25), and the median level of NT-proBNP was 2011 pg/ml (IQR, 579–7216). Thirty-four patients died during this study, and the 28-day mortality rate was 55.7%. Patients who die were older and had significantly (all p < 0.05) higher APACHE II scores and NT-proBNP levels than did patients who survived. Multivariate analysis identified age (HR: 1.546, 95% CI: 1.174–2.035, p = 0.0019) and NT-proBNP (HR: 1.009, 95% CI: 1.004–1.013, p = 0.0001) as significant risk factors of death. NT-proBNP was associated with poor outcomes for patients with ARDS, and its level predicted mortality. PMID:28322314

  15. Clinical value of plasma B-type natriuretic peptide assay in pediatric pneumonia accompanied by heart failure.

    PubMed

    Hu, Dan; Liu, Yang; Tao, Huixian; Gao, Jinping

    2015-12-01

    Previous studies have shown that B-type natriuretic peptide (BNP) is useful in differentiating cardiac from pulmonary causes of dyspnea in adults. To date, international guidelines have recommended measurements of circulating BNP as a biomarker for diagnostic and prognostic purposes, as well as therapeutic monitoring, in adults with cardiac diseases, particularly those suffering from acute and chronic heart failure (HF). The aim of the present study was to investigate the differential diagnostic and therapeutic analysis of BNP levels assayed in pediatric pneumonia accompanied by HF. The clinical data of 80 patients with pneumonia, aged 1-3 years, were analyzed. The patients were divided into two groups: Simple pneumonia (46 cases) and pneumonia accompanied by HF (34 cases). All patients underwent two plasma BNP assays: The first one upon admission to the hospital and the second one prior to discharge. The plasma BNP levels of 20 healthy children were used as the negative control. Plasma BNP levels were measured using the Triage® BNP automated immunoassay systems and reagents. Statistical analysis showed that the plasma BNP levels of the patients upon admission were higher in the pneumonia accompanied by HF group compared with those in the simple pneumonia group (750±120 vs. 135±50 pg/ml; P<0.05). In addition, in the pneumonia accompanied by HF group, the plasma BNP levels of the patients were higher upon admission to the hospital than they were prior to discharge (750±120 vs. 115±45 pg/ml; P<0.05); therefore, plasma BNP may comprise a sensitive diagnostic and therapeutic evaluative marker for pediatric patients with pneumonia accompanied by HF. This finding could prove invaluable in the clinical diagnosis and treatment of the disease.

  16. The prognostic value of N-terminal proB-type natriuretic peptide in patients with acute respiratory distress syndrome.

    PubMed

    Lai, Chih-Cheng; Sung, Mei-I; Ho, Chung-Han; Liu, Hsiao-Hua; Chen, Chin-Ming; Chiang, Shyh-Ren; Chao, Chien-Ming; Liu, Wei-Lun; Hsing, Shu-Chen; Cheng, Kuo-Chen

    2017-03-21

    We investigated whether N-terminal proB-type natriuretic peptide (NT-proBNP) predicts the prognosis of patients with acute respiratory distress syndrome (ARDS). Between December 1, 2012, and May 31, 2015, this observational study recruited patients admitted to our tertiary medical center who met the Berlin criteria for ARDS and who had their NT-proBNP measured. The main outcome was 28-day mortality. We enrolled 61 patients who met the Berlin criteria for ARDS: 7 were classified as mild, 29 as moderate, and 25 as severe. The median APACHE II scores were 23 (interquartile range [IQR], 18-28), and SOFA scores were 11 (IQR, 8-13). The median lung injury score was 3.0 (IQR, 2.50-3.25), and the median level of NT-proBNP was 2011 pg/ml (IQR, 579-7216). Thirty-four patients died during this study, and the 28-day mortality rate was 55.7%. Patients who die were older and had significantly (all p < 0.05) higher APACHE II scores and NT-proBNP levels than did patients who survived. Multivariate analysis identified age (HR: 1.546, 95% CI: 1.174-2.035, p = 0.0019) and NT-proBNP (HR: 1.009, 95% CI: 1.004-1.013, p = 0.0001) as significant risk factors of death. NT-proBNP was associated with poor outcomes for patients with ARDS, and its level predicted mortality.

  17. N-terminal pro b-type natriuretic peptide (NT-pro-BNP) –based score can predict in-hospital mortality in patients with heart failure

    PubMed Central

    Huang, Ya-Ting; Tseng, Yuan-Teng; Chu, Tung-Wei; Chen, John; Lai, Min-Yu; Tang, Woung-Ru; Shiao, Chih-Chung

    2016-01-01

    Serum N-terminal pro b-type natriuretic peptide (NT-pro-BNP) testing is recommended in the patients with heart failure (HF). We hypothesized that NT-pro-BNP, in combination with other clinical factors in terms of a novel NT-pro BNP-based score, may provide even better predictive power for in-hospital mortality among patients with HF. A retrospective study enrolled adult patients with hospitalization-requiring HF who fulfilled the predefined criteria during the period from January 2011 to December 2013. We proposed a novel scoring system consisting of several independent predictors including NT-pro-BNP for predicting in-hospital mortality, and then compared the prognosis-predictive power of the novel NT-pro BNP-based score with other prognosis-predictive scores. A total of 269 patients were enrolled in the current study. Factors such as “serum NT-pro-BNP level above 8100 mg/dl,” “age above 79 years,” “without taking angiotensin converting enzyme inhibitors/angiotensin receptor blocker,” “without taking beta-blocker,” “without taking loop diuretics,” “with mechanical ventilator support,” “with non-invasive ventilator support,” “with vasopressors use,” and “experience of cardio-pulmonary resuscitation” were found as independent predictors. A novel NT-pro BNP-based score composed of these risk factors was proposed with excellent predictability for in-hospital mortality. The proposed novel NT-pro BNP-based score was extremely effective in predicting in-hospital mortality in HF patients. PMID:27411951

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

    PubMed Central

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

    2017-01-01

    Background: While depression and certain cardiac biomarkers are associated with acute myocardial infarction (AMI), the relationship between them remains largely unexplored. We examined the association between depressive symptoms and biomarkers in patients with AMI. Methods: We performed a cross-sectional study using data from 103 patients with AMI between March 2013 and September 2014. The levels of depression, N-terminal proB-type natriuretic peptide (NT-proBNP), and troponin I (TnI) were measured at baseline. The patients were divided into two groups: those with depressive symptoms and those without depressive symptoms according to Zung Self-rating Depression Scale (SDS) score. Baseline comparisons between two groups were made using Student's t-test for continuous variables, Chi-square or Fisher's exact test for categorical variables, and Wilcoxon test for variables in skewed distribution. Binomial logistic regression and multivariate linear regression were performed to assess the association between depressive symptoms and biomarkers while adjusting for demographic and clinical variables. Results: Patients with depressive symptoms had significantly higher NT-proBNP levels as compared to patients without depressive symptoms (1135.0 [131.5, 2474.0] vs. 384.0 [133.0, 990.0], Z = −2.470, P = 0.013). Depressive symptoms were associated with higher NT-proBNP levels (odds ratio [OR] = 2.348, 95% CI: 1.344 to 4.103, P = 0.003) and higher body mass index (OR = 1.169, 95% confidence interval [CI]: 1.016 to 1.345, P = 0.029). The total SDS score was associated with the NT-proBNP level (β = 0.327, 95% CI: 1.674 to 6.119, P = 0.001) after multivariable adjustment. In particular, NT-proBNP was associated with three of the depressive dimensions, including core depression (β = 0.299, 95% CI: 0.551 to 2.428, P = 0.002), cognitive depression (β = 0.320, 95% CI: 0.476 to 1.811, P = 0.001), and somatic depression (β = 0.333, 95% CI: 0.240 to 0.847, P = 0.001). Neither the

  19. Mendelian Randomization Study of B-Type Natriuretic Peptide and Type 2 Diabetes: Evidence of Causal Association from Population Studies

    PubMed Central

    Pfister, Roman; Sharp, Stephen; Luben, Robert; Welsh, Paul; Barroso, Inês; Salomaa, Veikko; Meirhaeghe, Aline; Khaw, Kay-Tee; Sattar, Naveed; Langenberg, Claudia; Wareham, Nicholas J.

    2011-01-01

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

  20. B-type natriuretic peptide (BNP) and proBNP: role of emerging markers to guide therapy and determine prognosis in cardiovascular disorders.

    PubMed

    Godkar, Darshan; Bachu, Kalyan; Dave, Bijal; Niranjan, Selva; Khanna, Ashok

    2008-01-01

    Over the last decade, one group of neurohormonal markers, including atrial natriuretic peptide (ANP), N-terminal pro-ANP, B-type natriuretic peptide (BNP), and N-terminal proBNP, has generated much interest in the evaluation and management of heart failure and acute coronary syndrome. There has been so much literature on the subject, especially concerning BNP and proBNP, that it leaves us confused at times about what the literature has to say about these markers. In this article, we have made an honest attempt to examine all the available literature in relation to the impact of BNP and proBNP on cardiovascular disease and present it to the reader in an assimilated fashion.

  1. Hemoglobin and B-type natriuretic peptide preoperative values but not inflammatory markers, are associated with postoperative morbidity in cardiac surgery: a prospective cohort analytic study

    PubMed Central

    2013-01-01

    Introduction Risk stratification in cardiac surgery significantly impacts outcome. This study seeks to define whether there is an independent association between the preoperative serum level of hemoglobin (Hb), leukocyte count (LEUCO), high sensitivity C-reactive protein (hsCRP), or B-type natriuretic peptide (BNP) and postoperative morbidity and mortality in cardiac surgery. Methods Prospective, analytic cohort study, with 554 adult patients undergoing cardiac surgery in a tertiary cardiovascular hospital and followed up for 12 months. The cohort was distributed according to preoperative values of Hb, LEUCO, hsCRP, and BNP in independent quintiles for each of these variables. Results After adjustment for all covariates, a significant association was found between elevated preoperative BNP and the occurrence of low postoperative cardiac output (OR 3.46, 95% CI 1.53–7.80, p = 0.003) or postoperative atrial fibrillation (OR 3.8, 95% CI 1.45–10.38). For the combined outcome (death/acute coronary syndrome/rehospitalization within 12 months), we observed an OR of 1.93 (95% CI 1.00–3.74). An interaction was found between BNP level and the presence or absence of diabetes mellitus. The OR for non-diabetics was 1.26 (95% CI 0.61–2.60) and for diabetics was 18.82 (95% CI 16.2–20.5). Preoperative Hb was also significantly and independently associated with the occurrence of postoperative low cardiac output (OR 0.33, 95% CI 0.13–0.81, p = 0.016). Both Hb and BNP were significantly associated with the lengths of intensive care unit and hospital stays and the number of transfused red blood cells (p < 0.002). Inflammatory markers, although associated with adverse outcomes, lost statistical significance when adjusted for covariates. Conclusions High preoperative BNP or low Hb shows an association of independent risk with postoperative outcomes, and their measurement could help to stratify surgical risk. The ability to predict the onset of atrial fibrillation or

  2. Attenuation of monocyte chemotaxis--a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide.

    PubMed

    Glezeva, Nadezhda; Collier, Patrick; Voon, Victor; Ledwidge, Mark; McDonald, Kenneth; Watson, Chris; Baugh, John

    2013-08-01

    B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.

  3. Gene expression profiling of human hibernating myocardium: increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart.

    PubMed

    Prasad, Sanjay K; Clerk, Angela; Cullingford, Timothy E; Chen, Alexander W Y; Kemp, Timothy J; Cannell, Timothy M; Cowie, Martin R; Petrou, Mario

    2008-12-01

    A greater understanding of the molecular basis of hibernating myocardium may assist in identifying those patients who would most benefit from revascularization. Paired heart biopsies were taken from hypocontractile and normally-contracting myocardium (identified by cardiovascular magnetic resonance) from 6 patients with chronic stable angina scheduled for bypass grafting. Gene expression profiles of hypocontractile and normally-contracting samples were compared using Affymetrix microarrays. The data for patients with confirmed hibernating myocardium were analysed separately and a different, though overlapping, set (up to 380) of genes was identified which may constitute a molecular fingerprint for hibernating myocardium. The expression of B-type natriuretic peptide (BNP) was increased in hypocontractile relative to normally-contracting myocardium. The expression of BNP correlated most closely with the expression of proenkephalin and follistatin 3, which may constitute additional heart failure markers. Our data illustrate differential gene expression in hypocontractile and/hibernating myocardium relative to normally-contracting myocardium within individual human hearts. Changes in expression of these genes, including increased relative expression of natriuretic and other factors, may constitute a molecular signature for hypocontractile and/or hibernating myocardium.

  4. N-terminal pro-B-type Natriuretic Peptide is a Major Predictor of the Development of Atrial Fibrillation: The Cardiovascular Health Study

    PubMed Central

    Patton, Kristen K.; Ellinor, Patrick T.; Heckbert, Susan R.; Christenson, Robert H.; DeFilippi, Christopher; Gottdiener, John S.; Kronmal, Richard A.

    2014-01-01

    Background Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and health care expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, atrial fibrillation, and mortality. Methods and Results The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5,445 Cardiovascular Health Study participants, using relative risk regression for predicting prevalent AF, and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95%CI 17.9, 913.3, p< 0.001); and adjusted prevalence ratio of 147 for the highest quintile (95% CI 20.4, 1064.3, p<0.001) compared to the lowest. After a median follow up of 10 years (maximum of 16 years), there were 1,126 cases of incident AF (a rate of 2.2 per 100 person years). NT-proBNP was highly predictive of incident AF with an unadjusted hazard ratio of 5.2 (95% CI 4.3, 6.4, p < 0.001) for the development of AF for the highest quintile compared to the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes, and heart failure; with an adjusted hazard ratio of 4.0 (CI 3.2, 5.0, p< 0.001). Conclusions In a community based population of older adults, NT-pro BNP was a remarkable predictor of incident AF, independent of any other previously described risk factor. PMID:19841297

  5. B-type natriuretic peptide (BNP), not ANP, is the principal cardiac natriuretic peptide in vertebrates as revealed by comparative studies.

    PubMed

    Takei, Yoshio; Inoue, Koji; Trajanovska, Sofie; Donald, John A

    2011-05-01

    The natriuretic peptide (NP) family consists of at least seven members; cardiac ANP, BNP and VNP and brain CNPs (CNP1-4). Phylogenetic and comparative genomic analyses showed that CNP4 is the ancestral molecule of the family, from which CNP3 and CNP1/2 were duplicated in this order, and that the three cardiac NPs were generated from CNP3 by tandem duplication. Seven members existed at the divergence of ray-finned fishes and lobe-finned fishes (tetrapods), but some of the NP genes have disappeared during the course of evolution. In ray-finned fishes, all three cardiac NPs exist in chondrostei and some migratory teleost species, but VNP is generally absent and ANP is absent in a group of teleosts (Beloniformes). In tetrapods, ANP and BNP are present in mammals and amphibians, but ANP is usually absent in reptiles and birds. Thus, BNP is a ubiquitous cardiac NP in bony fishes and tetrapods though elasmobranchs and cyclostomes have only CNP3/4 as a cardiac NP. Functional studies indicate that cardiac NPs are essential Na(+)-extruding hormones throughout vertebrates; they play critical roles in seawater (SW) adaptation in teleosts, while they are important volume-depleting hormones in mammals as water and Na(+) are regulated in parallel in terrestrial animals. In mammals, cardiac NPs become prominent in pathological conditions such as heart failure where they are used in diagnosis and treatment. Although the functional role of BNP has not yet been fully elucidated compared with ANP in non-mammalian vertebrates, it appears that BNP plays pivotal roles in the cardiovascular and body fluid regulation as shown in mammals. ANP has previously been recognized as the principal cardiac NP in mammals and teleosts, but comparative studies have revealed that BNP is the only cardiac NP that exists in all tetrapods and teleosts. This is an excellent example showing that comparative studies have created new insights into the molecular and functional evolution of a hormone family.

  6. Comparison of B-type natriuretic peptide and left ventricular dysfunction in patients with constrictive pericarditis undergoing pericardiectomy.

    PubMed

    Kapoor, Poonam Malhotra; Aggarwal, Vikram; Chowdhury, Ujjwal; Choudhury, Minati; Singh, Sarvesh Pal; Kiran, Usha

    2010-01-01

    Chronic constrictive pericarditis (CCP) due to tuberculosis has high morbidity and mortality in the periopeartive period following pericardiectomy because of left ventricular (LV) dysfunction. Brain-type natriuretic peptide (BNP) is considered a marker for both LV systolic and diastolic dysfunction. We undertook this prospective study in 24 patients, to measure the BNP levels and to compare it with transmitral Doppler flow velocities, that is, the E/A ratio (E = initial peak velocity during early diastolic filling and A = late peak flow velocity during atrial systole), as a marker of diastolic function and systolic parameters, pre- and post-pericardiectomy, at the time of discharge. The latter parameters have been taken as a flow velocity across the mitral valve on a transthoracic echo. There was a significant decrease in the mean values of log BNP (6.19 +/- 0.33 to 4.65 +/- 0.14) (P = 0.001) and E/A ratio (1.81 +/- 0.21 to 1.01 +/- 0.14) (P = 0.001) post pericardiectomy, with a positive correlation, r = 0.896 and 0.837, respectively, between the two values at both the time periods. There was significant improvement in the systolic parameters of the LV function, that is, stroke volume index, cardiac index, systemic vascular resistance index, and delivered oxygen index. However, no correlation was observed between these values and the BNP levels. We believe that BNP can be used as a marker for LV diastolic dysfunction in place of the E/A ratio in patients with CCP, undergoing pericardiectomy. However, more studies have to be performed for validation of the same.

  7. Role of galectin-3 and plasma B type-natriuretic peptide in predicting prognosis in discharged chronic heart failure patients.

    PubMed

    Feola, Mauro; Testa, Marzia; Leto, Laura; Cardone, Marco; Sola, Mario; Rosso, Gian Luca

    2016-06-01

    Galectin-3 demonstrated to be a robust independent marker of cardiovascular mid-term (18-month) outcome in heart failure (HF) patients. The objective of this study was to analyze the value of a predischarged determination of plasma galectin-3 alone and with plasma brain natriuretic peptide (BNP) in predicting mid-term outcome in frequent-flyers (FF) HF (≥2 hospitalization for HF/year)/dead patients discharged after an acute decompensated HF (ADHF) episode.All FF chronic HF subjects discharged alive after an ADHF were enrolled. All patients underwent a determination of BNP and galectin-3, a 6-minute walk test, and an echocardiogram within 48 hours upon hospital discharge. Death by any cause, cardiac transplantation, and worsening HF requiring readmission to hospital were considered cardiovascular events.Eighty-three patients (67 males, age 73.2 ± 8.6 years old) were analyzed (mean follow-up 11.6 ± 5.2 months; range 4-22 months). During the follow-up 38 events (45.7%) were scheduled: (13 cardiac deaths, 35 rehospitalizations for ADHF). According to medical history, in 33 patients (39.8%) a definition of FF HF patients was performed (range 2-4 hospitalization/year). HF patients who suffered an event (FF or death) demonstrated more impaired ventricular function (P = 0.037), higher plasma BNP (P = 0.005), and Gal-3 at predischarge evaluation (P = 0.027). Choosing adequate cut-off points (BNP ≥ 500 pg/mL and Gal-3 ≥ 17.6 ng/mL), the Kaplan-Meier curves depicted the powerful stratification using BNP + Gal-3 in predicting clinical course at mid-term follow-up (log rank 5.65; P = 0.017).Adding Gal-3 to BNP, a single predischarge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode.

  8. Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

    PubMed

    Minai, Kosuke; Komukai, Kimiaki; Arase, Satoshi; Nagoshi, Tomohisa; Matsuo, Seiichiro; Ogawa, Kazuo; Kayama, Yosuke; Inada, Keiichi; Tanigawa, Shin-Ichi; Takemoto, Tomoyuki; Sekiyama, Hiroshi; Date, Taro; Ogawa, Takayuki; Taniguchi, Ikuo; Yoshimura, Michihiro

    2013-07-01

    Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

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

    PubMed

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

    2015-07-01

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

  10. Screening value of N-terminal pro-B-type natriuretic peptide as a predictor of perioperative cardiac events after noncardiac surgery.

    PubMed

    Goei, Dustin; Poldermans, Don

    2010-09-01

    Preoperative cardiac risk assessment is the cornerstone of rationale perioperative management that guides invasive surgical interventions. In addition to clinical risk factors, a simple screening biomarker would be useful for identifying those surgical patients who might benefit from additional cardiac testing or therapeutic interventions. Preoperative plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are predictors of cardiac events after noncardiac surgery. NT–proBNP is synthesized in the ventricular myocardium in response to ventricular wall stress. To further increase the diagnostic accuracy of NT-proBNP for preoperative screening, it is important to identify confounding factors that influence NT-proBNP levels and their interaction with identifying risks for adverse cardiac events. Moreover, until now the available data from previous studies has been unable to consistently recognize the optimal discriminatory threshold for NT-proBNP. Currently, the ongoing DECREASE-VI study is conducted to evaluate whether current preoperative risk stratification can be improved by incorporating NT-proBNP measurements.

  11. Plasma B-type natriuretic peptide is a useful tool for assessing coronary heart disease risk in a Japanese general population.

    PubMed

    Hasegawa, Takuya; Asakura, Masanori; Eguchi, Kazuo; Asanuma, Hiroshi; Ohara, Takahiro; Kanzaki, Hideaki; Hashimura, Kazuhiko; Tomoike, Hitonobu; Kim, Jiyoong; Kitakaze, Masafumi

    2015-01-01

    B-type natriuretic peptide (BNP) has been reported to be associated with cardiovascular prognosis in a community-based population. In addition, accumulation of individual cardiovascular risk factors is important in predicting an individual's risk of future cardiovascular disease. However, there have been few reports showing that BNP is a comprehensive marker of the accumulation of cardiovascular risk factors. We studied 1530 community-dwelling subjects without obvious heart diseases or renal dysfunction (mean age 62 ± 15 years; 569 men and 961 women) who participated in an annual health checkup in a rural Japanese community. Coronary heart disease (CHD) risk was estimated, and patients were placed into the following three groups based on the Framingham function: low risk, moderate risk and high risk. The prevalence of moderate- and high-risk subjects for CHD rose in both genders with increasing plasma BNP levels. The area under the receiver operating characteristic curve showed a modest ability of plasma BNP levels to detect these subjects (0.755 and 0.700 for men and women, respectively). The optimal thresholds for the identification of subjects with moderate- and high-risk disease were BNP concentrations of 12.0 and 22.0 pg ml(-1), with sensitivities of 70% and 66% and specificities of 71% and 63% for men and women, respectively. In conclusion, subjects with high plasma BNP levels were at higher risk for CHD in a population without obvious heart disease or renal dysfunction.

  12. Diagnostic utility of plasma N-terminal pro-B-type natriuretic peptide and C-reactive protein levels in differential diagnosis of pericardial constriction and restrictive cardiomyopathy.

    PubMed

    Karaahmet, Tansu; Yilmaz, Fatih; Tigen, Kursat; Mutlu, Bulent; Cevik, Cihan; Basaran, Yelda

    2009-01-01

    The authors investigated the diagnostic utility of plasma N-terminal pro-B-type natriuretic peptide (NT proBNP) and C-reactive protein (CRP) levels in the differential diagnosis of constrictive pericarditis (CP) and restrictive cardiomyopathy (RC). Twenty-five patients with high clinical suspicion of either CP or RC were enrolled. Mean plasma NT proBNP levels were significantly higher in patients with RC compared to those with CP (2641 +/- 2902 pg/mL vs 628 +/- 678 pg/mL; P=.003). The NT proBNP level that provided the best sensitivity and specificity for the differentiation of CP and RC was 800 pg/mL. Mean CRP levels were higher in patients with CP than with RC (1.41 +/- 1.73 mg/dL vs 0.38 +/- 0.21 mg/dL; P=.03). The CRP level that provided the best sensitivity and specificity for the differentiation of CP and RC was 0.57 mg/dL. Plasma NT proBNP and CRP levels can be useful in the differential diagnosis of RC and CP.

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

    PubMed

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

    2015-12-01

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

  14. Changes in B-type Natriuretic Peptide and Related Hemodynamic Parameters Following a Fluid Challenge in Critically Ill Patients with Severe Sepsis or Septic Shock

    PubMed Central

    Omar, Shahed; Ali, Ahmad; Atiya, Yahya; Mathivha, Rudo Lufuno; Dulhunty, Joel M.

    2017-01-01

    Context: Severe sepsis or septic shock. Aims: The aim of this study is to examine the effect of a fluid challenge on the B-type natriuretic peptide (BNP) and the hemodynamic state. Settings and Design: This observational study was conducted in an intensivist-led academic, mixed medical-surgical Intensive Care Unit. Subjects and Methods: Focused transthoracic echocardiogram, plasma BNP, and hemodynamic measurements were recorded at baseline and following a 500 ml fluid challenge in thirty patients. Independent predictors of the percentage (%) change in stroke volume (SV) were sought. Next, these independent predictors were assessed for a relationship with the percentage change in BNP. Statistical Analysis Used: Multiple linear regressions, Wilcoxon rank-sum test, t-test, and Pearson's correlation were used. Data analysis was carried out using SAS. The 5% significance level was used. Results: Using a multiple regression models, the percentage increase in SV was independently predicted by the percentage increase in mean arterial pressure, left ventricular end-diastolic volume/dimension (LVEDV/LVEDd), ejection fraction, and a decrease in Acute Physiology and Chronic Health Evaluation II score (P < 0.0001). Preload, measured using LVEDV1 (before the fluid challenge) was significantly larger in the fluid nonresponders (%SV increase <15%) vs. the responders (%SV increase ≥15%). Finally, the percentage change in BNP was positively correlated with left ventricular size at end diastole LVEDd, r = 0.4, P < 0.035). Conclusions: An increase in BNP soon after a fluid challenge may have some predictive utility of a large LVEDd, which in turn can be used to independently predict the SV response to a fluid challenge.

  15. N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for Loss of Muscle Mass in Prevalent Hemodialysis Patients

    PubMed Central

    Ikeda, Misa; Takahashi, Keiko; Shishido, Kanji; Shibata, Takanori

    2016-01-01

    Protein-energy wasting (PEW) is common in hemodialysis (HD) patients. A recent study demonstrated that a high level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be associated with PEW in those patients. This prospective study aimed to assess the association of NT-proBNP with body composition and muscle loss. A cohort of prevalent HD patients (n = 238) was examined. Blood samples were obtained at baseline to measure high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), adiponectin and NT-proBNP. Nutritional status and changes in muscle mass were assessed by subjective global assessment, percentage creatinine generation rate (%CGR), creatinine index (CI) and lean body mass (LBM) estimated by dual-energy X-ray absorptiometry (DXA). The %CGR and CI were calculated five times for one year, and DXA was performed at baseline and one year later. Cardiac function was estimated by ultrasonography at baseline. NT-proBNP was significantly higher in HD patients with PEW. High NT-proBNP was associated with cardiac dysfunction, increased levels of hsCRP and IL-6, and serially decreased levels of the indexes for muscle mass. Multiple regression analysis adjusted with confounders showed that NT-proBNP was an independent predictor for decrease in LBM and serial lower levels of %CGR and CI. In conclusion, the present study demonstrated a novel association between NT-proBNP and muscle loss. NT-proBNP may be an independent biomarker for malnutrition in HD patients, especially in patients with muscles loss, regardless of chronic inflammation, cardiac dysfunction, or overhydration. PMID:27870908

  16. Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide.

    PubMed

    Centeno, José M; Marrachelli, Vannina G; Miranda, Luis; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Miranda, Francisco J; Alborch, Enrique

    2013-02-15

    The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabetic than in control rabbits. Endothelium removal did not modify the relaxation to BNP in control rabbits but increased this relaxation in diabetic rabbits. In control rabbits, indomethacin inhibited the BNP-induced relaxation in the presence and in the absence of endothelium. In diabetic rabbits, indomethacin did not modify the BNP-induced relaxation in arteries with endothelium and inhibited it in arteries without endothelium. In the presence of BNP the carotid artery released thromboxane A2 and prostacyclin, and the release of endothelial prostacyclin was inhibited in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to BNP, and these inhibitions were lower in diabetic than in control rabbits. In conclusion, our results provide a new understanding concerning the mechanisms of the diabetes-induced hyporeactivity of the carotid artery to BNP, that at least include the loss of endothelial prostacyclin and a reduced participation of ATP-sensitive K(+) channels (KATP) and voltage-sensitive K(+) channels (KV).

  17. Plasma B-type natriuretic peptide levels are poorly related to the occurrence of ischemia or ventricular arrhythmias during symptom-limited exercise in low-risk patients

    PubMed Central

    Porta, Andreu; Candell-Riera, Jaume; Agulló, Luis; Aguadé-Bruix, Santiago; de León, Gustavo; Figueras, Jaume; Garcia-Dorado, David

    2016-01-01

    Introduction The usefulness of B-type natriuretic peptide (BNP) as a marker of ischemia is controversial. BNP levels have predicted arrhythmias in various settings, but it is unknown whether they are related to exercise-induced ischemic ventricular arrhythmias. Material and methods We analyzed in 63 patients (64 ±14 years, 65% male, 62% with known coronary disease) undergoing exercise stress single-photon emission computed tomography (SPECT) the association between plasma BNP values (before and 15 min after exercise) and the occurrence of ischemia or ventricular arrhythmias during the test. Results Exercise test (8.1 ±2.7 min, 7.4 ±8.1 metabolic equivalents, 82 ±12% of maximal predicted heart rate) induced reversible perfusion defects in 23 (36%) patients. Eight (13%) patients presented significant arrhythmias (≥ 7 ventricular premature complexes/min, couplets, or non-sustained ventricular tachycardia during exercise or in the first minute of recovery). Median baseline BNP levels were 17.5 (12.4–66.4) pg/ml in patients developing scintigraphic ischemia and 45.6 (13.2–107.4) pg/ml in those without ischemia (p = 0.137). The BNP levels increased after exercise (34.4 (15.3–65.4)% increment over baseline, p < 0.001), but the magnitude of this increase was not related to SPECT positivity (35.7 (18.8–65.4)% vs. 27.9 (5.6–64.0)% in patients with and without ischemia, respectively, p = 0.304). No significant association was found between BNP values (at baseline or their change during the test) and ventricular arrhythmias. Conclusions Plasma BNP values – at baseline or after exercise – were not associated with myocardial ischemia or with ventricular arrhythmia during exercise SPECT. These results highlight the limited usefulness of this biomarker to assess acute ischemia. PMID:27186178

  18. Diagnostic and prognostic utilities of multimarkers approach using procalcitonin, B-type natriuretic peptide, and neutrophil gelatinase-associated lipocalin in critically ill patients with suspected sepsis

    PubMed Central

    2014-01-01

    Background We investigated the diagnostic and prognostic utilities of procalcitonin (PCT), B-type natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in critically ill patients with suspected sepsis, for whom sepsis was diagnosed clinically or based on PCT concentrations. Methods PCT, BNP, and NGAL concentrations were measured in 340 patients and were followed up in 109 patients. All studied biomarkers were analyzed according to the diagnosis, severity, and clinical outcomes of sepsis. Results Clinical sepsis and PCT-based sepsis showed poor agreement (kappa = 0.2475). BNP and NGAL showed significant differences between the two groups of PCT-based sepsis (P = 0.0001 and P < 0.0001), although there was no difference between the two groups of clinical sepsis. BNP and NGAL were significantly different according to the PCT staging and sepsis-related organ failure assessment subscores (P < 0.0001, all). BNP and PCT concentrations were significantly higher in the non-survivors than in the survivors (P = 0.0002) and showed an equal ability to predict in-hospital mortality (P = 0.0001). In the survivors, the follow-up NGAL and PCT concentrations were significantly lower than the initial values (148.7 ng/mL vs. 214.5 ng/mL, P < 0.0001; 0.61 ng/mL vs. 5.56 ng/mL, P = 0.0012). Conclusions PCT-based sepsis diagnosis seems to be more reliable and discriminating than clinical sepsis diagnosis. Multimarker approach using PCT, BNP, and NGAL would be useful for the diagnosis, staging, and prognosis prediction in the critically ill patients with suspected sepsis. PMID:24761764

  19. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy.

    PubMed

    Dunn, Michael E; Manfredi, Thomas G; Agostinucci, Kevin; Engle, Steven K; Powe, Josh; King, Nicholas M P; Rodriguez, Luis A; Gropp, Kathryn E; Gallacher, Matthew; Vetter, Frederick J; More, Vijay; Shimpi, Prajakta; Serra, David; Colton, Heidi M

    2017-02-01

    Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

  20. N-Terminal Pro-B-Type Natriuretic Peptide Plasma Levels as a Potential Biomarker for Cardiac Damage After Radiotherapy in Patients With Left-Sided Breast Cancer

    SciTech Connect

    D'Errico, Maria P.; Grimaldi, Luca; Petruzzelli, Maria F.; Gianicolo, Emilio A.L.; Tramacere, Francesco; Monetti, Antonio; Placella, Roberto; Pili, Giorgio; Andreassi, Maria Grazia; Sicari, Rosa; Picano, Eugenio; Portaluri, Maurizio

    2012-02-01

    Purpose: Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer. Methods and Materials: NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography. Results: NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7-333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0-172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V{sub 3Gy}(%) (p = 0.001), the ratios D{sub 15cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.01), the ratios D{sub 15cm}{sup 3}/D{sub 50%} (Gy) (p = 0.008) for the heart and correlations between plasma levels and V{sub 2Gy} (%) (p = 0.002), the ratios D{sub 1cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.03), and the ratios D{sub 0.5cm{sup 3}}(Gy)/D{sub 50%}(Gy) (p = 0.05) for the ventricle. Conclusions: Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non-RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small

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

    PubMed Central

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

    2016-01-01

    Objective Monitoring B-type natriuretic peptide (BNP) to guide pharmacotherapy might improve survival in patients with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). However, the cost-effectiveness of BNP-guided care is uncertain and guidelines do not uniformly recommend it. We assessed the cost-effectiveness of BNP-guided care in patient subgroups defined by age and ejection fraction. Methods We used a Markov model with a 3-month cycle length to estimate the lifetime health service costs, quality-adjusted life years (QALYs) and incremental net monetary benefits (iNMBs) of BNP-guided versus clinically guided care in 3 patient subgroups: (1) HFrEF patients <75 years; (2) HFpEF patients <75 years; and (3) HFrEF patients ≥75 years. There is no evidence of benefit in patients with HFpEF aged ≥75 years. We used individual patient data meta-analyses and linked primary care, hospital and mortality data to inform the key model parameters. We performed probabilistic analysis to assess the uncertainty in model results. Results In younger patients (<75 years) with HFrEF, the mean QALYs (5.57 vs 5.02) and costs (£63 527 vs £58 139) were higher with BNP-guided care. At the willingness-to-pay threshold of £20 000 per QALY, the positive iNMB (£5424 (95% CI £987 to £9469)) indicates that BNP-guided care is cost-effective in this subgroup. The evidence of cost-effectiveness of BNP-guided care is less strong for younger patients with HFpEF (£3155 (−£10 307 to £11 613)) and older patients (≥75 years) with HFrEF (£2267 (−£1524 to £6074)). BNP-guided care remained cost-effective in the sensitivity analyses, albeit the results were sensitive to assumptions on its sustained effect. Conclusions We found strong evidence that BNP-guided care is a cost-effective alternative to clinically guided care in younger patients with HFrEF. It is potentially cost-effective in younger patients with HFpEF and older

  2. N-Terminal pro-B-Type Natriuretic Peptide Levels are Linked with Modified Child-Pugh Classification in Patients with Nonalcoholic Cirrhosis [NT-ProBNP and Liver Cirrhosis].

    PubMed

    Kumbasar, Abdulbaki; Navdar, Mehtap; Ataoglu, Esra; Uzunhasan, Isil; Ergen, Kadir; Poturoglu, Sule; Basinoglu, Filiz; Yilmaz, Fatih; Yenigun, Mustafa; Sar, Fuat; Tanriverdi, Ozgur

    2017-03-01

    Excess N-terminal pro-brain natriuretic peptide secretion has been linked to cirrhosis in previously studies. The relationship of plasma N-terminal pro-brain natriuretic peptide levels and cardiac dysfunction determined by echocardiography were investigated in patients with nonalcoholic cirrhosis and a control group of chronic hepatitis. This study was designed as a cross-sectional study. Thirty-two men and thirty-three women who gave informed consent who were followed-up for chronic liver failure were enrolled. All patients gave clinical history, physical examination was carried out and information about ongoing medication has been obtained. Serum N-terminal pro-brain natriuretic peptide level was measured in all patients. The same cardiologist determined ejection fraction, end-diastolic left ventricular diameter, interventricular septum, and posterior wall on transthoracic echocardiography. Patients with extensive liver disease according to Child-Pugh classification from A to C had increasing N-terminal pro-brain natriuretic peptide levels in association (P < .001). According to the Child-Pugh classification there were no significant difference between groups for echocardiographic measurements (P > .05). N-terminal pro-brain natriuretic peptide may be an important marker for cardiac dysfunction in patients with chronic liver failure in accordance with Child-Pugh stage.

  3. Resting and dobutamine stress test induced serum concentrations of brain natriuretic peptide in German Shepherd dogs.

    PubMed

    Spasojević Kosić, Ljubica; Trailović, Dragiša R; Matunović, Radomir

    2012-12-01

    Studies of clinical uses of brain natriuretic peptide (BNP) represent one of the most important advances in cardiology since the introduction of echocardiography as a clinical diagnostic procedure. Defining the clinical potential of BNP in canine cardiology has not been completed yet. The aim of this study is to measure BNP concentrations in healthy German Shepherd dogs of different ages as a baseline in resting and when conventional protocol of the dobutamine stress test (DST) is applied to dogs. Concentrations of BNP were measured in blood serum by the radioimmunoassay method. The values of BNP concentrations were compared to cardiac parameters obtained by standard cardiac diagnostic procedures (radiology, electrocardiography and echocardiography). No significant differences in serum BNP concentrations existed in dogs of different ages. A statistically significant increase in BNP concentrations was registered after DST. These changes in BNP concentrations were related to ST/T electrocardiographic changes, and correlated to changes in the left ventricular internal diameter in systole (LVESD). These data suggest that BNP is not increased in aged dogs with normal cardiac systolic function and renal function, and that myocardial ischemia leads to a significant increase in BNP concentrations even in dogs with normal left ventricular function.

  4. The natriuretic peptides.

    PubMed

    Baxter, Gary F

    2004-03-01

    The natriuretic peptides are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of actions throughout the body. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their volume regulating effects. These pleiotropic actions include local (autocrine/paracrine) regulatory actions of ANP and BNP within the heart, and of another natriuretic peptide, CNP, within the vessel wall. Effects on function and growth of the local tissue environment are likely to be of great importance, especially in disease states where tissue and circulating levels of ANP and BNP rise markedly. At present, the relevance of other natriuretic peptides (notably uroguanylin and DNP) to human physiology and pathology remain uncertain. Other articles in this issue of Basic Research in Cardiology review the molecular physiology of natriuretic peptide signalling, with a particular emphasis on the lessons from genetically targetted mice; the vascular activity of natriuretic peptides; the regulation and roles of natriuretic peptides in ischaemic myocardium; and the diagnostic, prognostic and therapeutic roles of natriuretic peptides in heart failure.

  5. Effects of Exercise Training versus Attention on Plasma B-type Natriuretic Peptide, 6-Minute Walk Test and Quality of Life in Individuals with Heart Failure

    PubMed Central

    Norman, Joseph F.; Pozehl, Bunny J.; Duncan, Kathleen A.; Hertzog, Melody A.; Krueger, Steven K.

    2012-01-01

    Purpose The purpose of this study was to compare an Exercise Training Group (EX) with an Attention-Control Group (AT-C) to more specifically assess the impact of exercise training on individuals with heart failure (HF). Methods Forty-two individuals with HF were randomized to AT-C or EX that met with the same frequency and format of investigator interaction. Baseline, 12- and 24-week measurements of B-type naturetic peptide (BNP), 6-minute walk test (6-MWT), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) were obtained. Results BNP tended to increase in the AT-C while remaining stable in the EX over time. A clinically significant increase in 6-MWT was demonstrated by the EX but not the AT-C. The EX achieved a clinically significant change on the KCCQ at 12 weeks, with further improvement by 24 weeks, while the AT-C demonstrated a clinically significant change at 24 weeks. Conclusions Attention alone was inadequate to positively impact BNP levels or 6-MWT distances, but did have a positive impact on quality of life after 24 weeks. Although exercise offers enhanced benefits, individuals with HF unable to participate in an exercise program may still gain quality of life benefits from participation in a peer-support group that discusses topics pertinent to HF. PMID:23304096

  6. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    PubMed Central

    Fattouh, Aya M; El-Shabrawi, Mortada H; Mahmoud, Enas H; Ahmed, Wafaa O

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue Doppler imaging. Results: Patients’ mean ages were 7.66 ± 4.16 years (vs. 6.88 ± 3.04 years for the controls). The study included 27 males and 25 females (28 and 25 respectively for the controls). Patients had larger left atrium and right ventricle (RV) (P value 0.05) and increased LV posterior wall thickness than controls (P value 0.04). They had higher late atrial diastolic filling velocity (A) of tricuspid valve (TV) inflow (0.59 ± 0.17 vs. 0.5 ± 0.1 m/s, P < 0.001) and lower ratios between the early diastolic filling velocity (E) and A wave velocity (E/A) of both mitral valve and TV inflow (1.7 ± 0.35 vs. 1.87 ± 0.34 and 1.3 ± 0.3 vs. 1.5 ± 0.3, P < 0.005 and 0.0008, respectively). Patients had significantly longer isovolumic relaxation time of LV (45.5 ± 11.1 vs. 40.5 ± 7.7 ms P 0.008), higher late diastolic peak myocardial velocity (A’) (11.8 ± 3.6 vs. 9.5 ± 2.7 ms, P 0.0003) and systolic velocity (S’) of the RV (14.5 ± 2.7 vs. 13.2 ± 2.9, P 0.01) and significantly higher myocardial performance index of both LV and RV (P 0.001 and 0.01). BNP levels were significantly higher in cases than controls (5.25 ng/l vs. 3.75 ng/l, P < 0.04) and was correlated with the E wave velocity of the TV (r 0.004) and the E/E’ ratio of the RV (r 0.001). None of the clinical or laboratory data were correlated with the BNP level. Conclusion Cirrhotic children have cardiac dysfunction mainly in the form of diastolic dysfunction. There is a need that CCM be more accurately

  7. Natriuretic peptide metabolism, clearance and degradation.

    PubMed

    Potter, Lincoln R

    2011-06-01

    Atrial natriuretic peptide, B-type natriuretic peptide and C-type natriuretic peptide constitute a family of three structurally related, but genetically distinct, signaling molecules that regulate the cardiovascular, skeletal, nervous, reproductive and other systems by activating transmembrane guanylyl cyclases and elevating intracellular cGMP concentrations. This review broadly discusses the general characteristics of natriuretic peptides and their cognate signaling receptors, and then specifically discusses the tissue-specific metabolism of natriuretic peptides and their degradation by neprilysin, insulin-degrading enzyme, and natriuretic peptide receptor-C.

  8. Prognostic value of tissue Doppler right ventricular systolic and diastolic function indexes combined with plasma B-type natriuretic Peptide in patients with advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

    PubMed

    Bistola, Vasiliki; Parissis, John T; Paraskevaidis, Ioannis; Panou, Fotios; Nikolaou, Maria; Ikonomidis, Ignatios; Flessas, Nikolaos; Filippatos, Gerasimos; Iliodromitis, Efstathios; Kremastinos, Dimitrios T

    2010-01-15

    Right ventricular (RV) dysfunction adversely affects prognosis in patients with chronic heart failure (CHF) due to left ventricular (LV) dysfunction. However, little evidence exists regarding the prognostic role of RV systolic and diastolic function indexes in combination with plasma B-type natriuretic peptide (BNP) in advanced CHF. Thus, 102 consecutive hospitalized patients with advanced CHF (New York Heart Association classes III to IV) due to LV systolic dysfunction (LV ejection fraction <35%) were studied by 2-dimensional conventional and tissue Doppler imaging (TDI) echocardiography of the left and right ventricles. Plasma BNP was also measured. Patients were followed for 6 months for major cardiovascular events (cardiovascular death and/or CHF-related hospitalization). During follow-up, 13 patients died and 63 patients reached the combined end point of cardiovascular death or CHF-related hospitalization. By univariate analysis, RV TDI systolic velocity, dilated cardiomyopathy, digoxin treatment (all p values <0.01), and female gender (p <0.05) were associated with increased cardiovascular death. Transmitral Doppler to mitral annular TDI early diastolic velocity ratio, RV TDI early diastolic velocity (p <0.05), and ratio of early to late RV diastolic TDI velocities (p <0.01) predicted the combined end point. In multivariate analysis, decreased RV systolic velocity, dilated cardiomyopathy, and female gender (all p values <0.05) were independent predictors of cardiovascular death, whereas increased ratio of early to late RV diastolic TDI velocities (p <0.01) and increased BNP (p <0.05) predicted the combined end point. In conclusion, RV TDI indexes combined with increased plasma BNP additively predict adverse cardiac outcomes in advanced CHF.

  9. Role of Right Ventricular Dysfunction and Diabetes Mellitus in N-terminal pro-B-type Natriuretic Peptide Response of Patients With Severe Mitral Regurgitation and Heart Failure After MitraClip.

    PubMed

    Kaneko, Hidehiro; Neuss, Michael; Weissenborn, Jens; Butter, Christian

    2017-04-06

    MitraClip (MC) is an alternative therapeutic option for patients with severe mitral regurgitation (MR) who are at high surgical risk. Most candidates for MC have severe heart failure (HF) with increased N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels. We sought to clarify the response of NT-pro BNP after MC and to identify the determinants of NT-pro BNP nonresponders. Among 136 consecutive patients successfully treated with MC, we excluded 20 patients due to low baseline NT-pro BNP levels and therefore examined 116 patients. NT-pro BNP responders were defined as patients whose NT-pro BNP levels decreased by > 30% at 6 months after MC. Mean NT-pro BNP levels significantly decreased from 6,117 pg/mL at baseline to 4,143 pg/mL at 6 months after MC (P < 0.001); 61 patients (53%) were responders. Diabetes mellitus (DM) (51% versus 25%; P = 0.003) and atrial fibrillation (67% versus 49%; P = 0.049) were more common in nonresponders. Baseline New York Heart Association (NYHA) class and NT-proBNP levels were higher in responders. Right ventricular systolic dysfunction (RVSD) defined as tricuspid annular plane systolic excursion (TAPSE) < 15 mm was more common in nonresponders (41% versus 18%; P = 0.008). Multivariable logistic regression analysis revealed that DM (odds ratio [OR], 2.966; P = 0.014), RVSD (OR, 3.948; P = 0.006), and baseline NT-proBNP > 5,000 pg/mL (OR, 0.204; P = 0.001) were independent determinants of nonresponders. All-cause death tended to be less common in responders to NT-pro BNP (20% versus 31%; P = 0.163). In conclusion, NT-pro BNP levels significantly decreased after MC. DM and RVSD were determinants of NT-pro BNP nonresponse after the MC procedure.

  10. B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina

    PubMed Central

    2011-01-01

    Background Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. Methods We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. Results 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively. The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. Conclusion BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS. Trial Registration ClinicalTrials.gov Identifier: NCT01377402. PMID:21958326

  11. Serial measurement of N-terminal pro-B-type natriuretic peptide and cardiac troponin T for cardiovascular disease risk assessment in the Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Daniels, Lori B.; Clopton, Paul; deFilippi, Christopher R.; Sanchez, Otto; Bahrami, Hossein; Lima, Joao A. C.; Tracy, Russell P.; Siscovick, David; Bertoni, Alain G.; Greenland, Philip; Cushman, Mary; Maisel, Alan S.; Criqui, Michael H.

    2015-01-01

    Background N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (TnT) predict cardiovascular disease (CVD) risk in a variety of populations. Whether their predictive value varies by ethnicity is unknown. We sought to determine: whether NT-proBNP and TnT improve prediction of incident coronary heart disease (CHD) and CVD, independent of CVD risk factors, in a multi-ethnic population; whether NT-proBNP improves prediction compared to the Framingham Risk Score (FRS) or the Pooled Cohort Risk Equation (PCRE); and whether a second NT-proBNP further improves prediction. Methods NT-proBNP and TnT were measured in 5592 Multi-Ethnic Study of Atherosclerosis white, black, Hispanic and Chinese participants (60% nonwhite, mean age 62.3±10.3) in 2000–2002 and 2004–2005. We evaluated adjusted risk of incident CHD and CVD based on baseline and change in biomarker concentration. Results Participants were followed through 2011 and incurred 370 CVD events (232 CHD). NT-proBNP and TnT concentrations varied by ethnicity. NT-proBNP and TnT were associated with an increased risk of events (adjusted HR for CHD [95% CI] for 5th versus other 4 quintiles of NT-proBNP, 2.03[1.50–2.76]; HR for CHD for detectable versus undetectable TnT, 3.95[2.29–6.81]). NT-proBNP improved risk prediction and classification compared to the FRS and the PCRE. Change in NT-proBNP was independently associated with events (HR for CHD per unit increase in ΔlogNT-proBNP, 1.95[1.16–3.26]). None of the observed associations varied by ethnicity. Conclusions NT-proBNP and TnT are predictors of incident CHD, independent of established risk factors and ethnicity, in a multi-ethnic population without known CVD. Change in NT-proBNP may add additional prognostic information. PMID:26678639

  12. Combination of high-sensitivity troponin I and N-terminal pro-B-type natriuretic peptide predicts future hospital admission for heart failure in high-risk hypertensive patients with preserved left ventricular ejection fraction.

    PubMed

    Okuyama, Ryunosuke; Ishii, Junnichi; Takahashi, Hiroshi; Kawai, Hideki; Muramatsu, Takashi; Harada, Masahide; Yamada, Akira; Motoyama, Sadako; Matsui, Shigeru; Naruse, Hiroyuki; Sarai, Masayoshi; Hasegawa, Midori; Watanabe, Eiichi; Suzuki, Atsushi; Hayashi, Mutsuharu; Izawa, Hideo; Yuzawa, Yukio; Ozaki, Yukio

    2017-02-02

    Additional risk stratification may provide more aggressive and focalized preventive treatment to high-risk hypertensive patients according to the Japanese hypertension guidelines. We prospectively investigated the predictive value of high-sensitivity troponin I (hsTnI), both independently and in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP), for incident heart failure (HF) in high-risk hypertensive patients with preserved left ventricular ejection fraction (LVEF). Baseline hsTnI and NT-proBNP levels and echocardiography data were obtained for 493 Japanese hypertensive outpatients (mean age, 68.5 years) with LVEF ≥ 50%, no symptomatic HF, and at least one of the following comorbidities: stage 3-4 chronic kidney disease, diabetes mellitus, and stable coronary artery disease. During a mean follow-up period of 86.1 months, 44 HF admissions occurred, including 31 for HF with preserved ejection fraction (HFpEF) and 13 for HF with reduced ejection fraction (HFrEF; LVEF <50%). Both hsTnI (p < 0.01) and NT-proBNP (p < 0.005) levels were significant independent predictors of HF admission. Furthermore, when the patients were stratified into 4 groups according to increased hsTnI (≥highest tertile value of 10.6 pg/ml) and/or increased NT-proBNP (≥highest tertile value of 239.7 pg/ml), the adjusted relative risks for patients with increased levels of both biomarkers versus neither biomarker were 13.5 for HF admission (p < 0.0001), 9.45 for HFpEF (p = 0.0009), and 23.2 for HFrEF (p = 0.003). Finally, the combined use of hsTnI and NT-proBNP enhanced the C-index (p < 0.05), net reclassification improvement (p = 0.0001), and integrated discrimination improvement (p < 0.05) to a greater extent than that of any single biomarker. The combination of hsTnI and NT-proBNP, which are individually independently predictive of HF admission, could improve predictions of incident HF in high-risk hypertensive patients but could

  13. FACTORS ASSOCIATED WITH SERUM BRAIN NATRIURETIC PEPTIDE LEVELS AFTER THE FONTAN PROCEDURE

    PubMed Central

    Atz, Andrew M.; Zak, Victor; Breitbart, Roger E.; Colan, Steven D.; Pasquali, Sara K.; Hsu, Daphne T.; Lu, Minmin; Mahony, Lynn; Paridon, Stephen M.; Puchalski, Michael D.; Geva, Tal; McCrindle, Brian W.

    2011-01-01

    Objective Although a useful marker of heart failure in adults, the utility of brain natriuretic peptide concentration (BNP) for children after the Fontan procedure is not well studied. Design BNP was measured in 510 patients aged 6–18 years in the Pediatric Heart Network Fontan cross-sectional study at a median of 8.2 years after Fontan. Patients underwent echocardiography, exercise testing, magnetic resonance imaging (MRI) and functional health status questionnaires. Associations of BNP with baseline patient characteristics, medical history and cross-sectional assessment were examined with multivariable linear regression analyses. Results The distribution of BNP was highly skewed, median 13.0 pg/mL (inter-quartile range: 7.1, 25.9), and was normalized with logarithmic transformation (logBNP). Among medical history variables, logBNP was greater in females (p=0.02) and older patients (p<0.001). Presence of pre-Fontan systolic ventricular dysfunction, greater number of post-Fontan complications, and thrombosis after Fontan were independently associated with higher logBNP (R2=0.16). Age-adjusted logBNP was significantly related to Fontan connection type, (lower with extracardiac conduits, higher with atriopulmonary connection; p<0.001). Lower physical functioning health status (R2=0.05), lower chronotropic index during exercise (R2=0.17), indices of diastolic dysfunction measured by echocardiography (R2=0.15), and higher total ventricular mass on MRI (R2=0.33) were related to higher logBNP. Conclusions Despite a markedly abnormal circulation, BNP was variable but within a normal range in the majority of Fontan patients in this large outpatient cohort. Higher BNP was associated with several markers of suboptimal outcome, although associations were weak. The routine use of BNP as an outpatient surveillance tool in asymptomatic Fontan patients is not warranted. PMID:21435188

  14. Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic factor in heart failure: a double blind, randomised comparison of metoprolol and a third generation vasodilating beta blocker.

    PubMed Central

    Sanderson, J. E.; Chan, W. W.; Hung, Y. T.; Chan, S. K.; Shum, I. O.; Raymond, K.; Woo, K. S.

    1995-01-01

    OBJECTIVES--This study examines the acute effects of two differing beta adrenergic blocking agents (metoprolol and a third generation vasodilating beta blocker) on plasma concentrations of atrial natriuretic factor (ANF), brain (ventricular) natriuretic factor (BNF), and haemodynamic variables in patients with heart failure. SETTING--University teaching hospital. METHODS--20 patients with impaired left ventricular systolic function [ejection fraction 32 (SEM 2.3)%] were randomised in a double blind manner to receive either oral metoprolol 6.25 mg twice daily or celiprolol 25 mg daily. Haemodynamic variables were evaluated by Swan-Ganz pulmonary artery catheter over 24 hours. ANF and BNF concentrations were measured at baseline, 5 h, and 24 h by radioimmunoassay. RESULTS--At baseline ANF and BNF concentrations were considerably raised compared to the normal range. Treatment with metoprolol caused ANF to rise further to 147% of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029). This was associated with a small but non-significant rise in pulmonary capillary wedge pressure. Cardiac output and systemic vascular resistance were unchanged at 24 h. In contrast, after celiprolol ANF fell to 90% of basal levels at 5 h and to 74% of basal level at 24 h (P = 0.019), associated with a small but non-significant fall in pulmonary capillary wedge pressure [-3.3 (2.7) mm Hg] and systemic vascular resistance, and rise in cardiac output from 3.2 (0.2) to 4.0 (0.4) l/min (P = 0.04). BNF concentrations rose to 112% of baseline at 5 h (P = 0.09) after metoprolol but fell slightly, to 91% of baseline values, after celiprolol (NS). CONCLUSIONS--Metoprolol, even in very low doses (6.25 mg), produced a rise in ANF and BNF, although minimal haemodynamic changes were detected. In contrast, a vasodilating beta blocker was associated with a significant fall in ANF and BNF and a small rise in cardiac output. This study confirms both the advantages of vasodilating beta blockers

  15. Relation of N-Terminal Pro-B-Type Natriuretic Peptide and Left Ventricular Diastolic Function to Exercise Tolerance in Patients With Significant Valvular Heart Disease and Normal Left Ventricular Systolic Function.

    PubMed

    Hwang, Ji-Won; Park, Sung-Ji; Cho, Eun Jeong; Kim, Eun Kyoung; Lee, Ga Yeon; Chang, Sung-A; Choi, Jin-Oh; Lee, Sang-Chol; Park, Seung Woo

    2017-03-16

    An association between N-terminal prohormone brain natriuretic peptide (NT-proBNP) and exercise tolerance in patients with valvular heart disease (VHD) has been suggested; however, there are few data available regarding this relation. The aim of this study is to evaluate the correlation between exercise tolerance and NT-proBNP in patients with asymptomatic or mildly symptomatic significant VHD and normal left ventricular ejection fraction (LV EF). A total of 96 patients with asymptomatic or mildly symptomatic VHD and normal LV EF (≥50%) underwent cardiopulmonary exercise echocardiography. NT-proBNP levels were determined at baseline and after exercise in 3 hours. Patients were divided in 2 groups based on lower (<26 ml/kg/min, n = 47) or higher (≥26 ml/kg/min, n = 49) peak oxygen consumption (VO2) as a representation of exercise tolerance. In the 2 groups, after adjusting for age and gender, the NT-proBNP level after exercise in 3 hours, left atrial volume index before exercise, right ventricular systolic pressure before exercise, E velocity after exercise, and E/e' ratio after exercise varied significantly. In addition, peak VO2 was inversely related to NT-proBNP before (r = -0.352, p <0.001) and after exercise (r = -0.351, p <0.001). The NT-proBNP level before exercise was directly related to the left atrial volume index, E/e' ratio, and right ventricular systolic pressure before and after exercise. NT-proBNP after exercise was also directly related to the same parameters. NT-proBNP levels both before and after exercise were higher in the group with lower exercise tolerance. In conclusion, through the correlation among exercise tolerance, NT-proBNP, and parameters of diastolic dysfunction, we demonstrated that diastolic dysfunction and NT-proBNP could predict exercise tolerance in patients with significant VHD and normal LV EF.

  16. The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting

    PubMed Central

    Roberts, Emmert; Dworzynski, Katharina; Al-Mohammad, Abdallah; Cowie, Martin R; McMurray, John J V; Mant, Jonathan

    2015-01-01

    Objectives To determine and compare the diagnostic accuracy of serum natriuretic peptide levels (B type natriuretic peptide, N terminal probrain natriuretic peptide (NTproBNP), and mid-regional proatrial natriuretic peptide (MRproANP)) in people presenting with acute heart failure to acute care settings using thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure. Design Systematic review and diagnostic meta-analysis. Data sources Medline, Embase, Cochrane central register of controlled trials, Cochrane database of systematic reviews, database of abstracts of reviews of effects, NHS economic evaluation database, and Health Technology Assessment up to 28 January 2014, using combinations of subject headings and terms relating to heart failure and natriuretic peptides. Eligibility criteria for selecting studies Eligible studies evaluated one or more natriuretic peptides (B type natriuretic peptide, NTproBNP, or MRproANP) in the diagnosis of acute heart failure against an acceptable reference standard in consecutive or randomly selected adults in an acute care setting. Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or report age independent natriuretic peptide thresholds. Studies not available in English were also excluded. Results 37 unique study cohorts described in 42 study reports were included, with a total of 48 test evaluations reporting 15 263 test results. At the lower recommended thresholds of 100 ng/L for B type natriuretic peptide and 300 ng/L for NTproBNP, the natriuretic peptides have sensitivities of 0.95 (95% confidence interval 0.93 to 0.96) and 0.99 (0.97 to 1.00) and negative predictive values of 0.94 (0.90 to 0.96) and 0.98 (0.89 to 1.0), respectively, for a diagnosis of acute heart failure. At the lower recommended threshold of 120 pmol/L, MRproANP has a sensitivity ranging from 0.95 (range 0

  17. Serum atrial natriuretic peptide (ANP) as an objective indicator for the diagnosis of neurogenic shock: animal experiment and human case report.

    PubMed

    Zhao, Min-Zhu; Li, Yong-Guo; Zhang, Peng; Xiong, Jin-Cheng; Zhu, Shi-Sheng; Xiao, Xuan; Li, Jian-Bo

    2017-03-01

    In forensic medicine, the diagnosis of death due to neurogenic shock is considered to be an aporia, as lacking objective indicators and presenting atypical symptoms in autopsy. Medico-legal disputes and complaints occasionally result from this ambiguity. To explore potential objective indicators of neurogenic shock, we set up a model of neurogenic shock by applying an external mechanical force on the carotid sinus baroreceptor in rabbits. The serum atrial natriuretic peptide (ANP) level was measured by radioimmunoassay in the control group (n = 8), survival group (n = 15) and death group (n = 5) both before and after the insult. The serum ANP level showed a significant increase after the insult in the death group compared with the serum obtained before the insult (P = 0.006), while the serum ANP level after the insult in the survival group and control group was not statistically significant compared with the serum obtained before the insult (P = 0.332 and P = 0.492, respectively). To verify the repeatability of the model and the postmortem behavior of serum ANP, five healthy adult rabbits underwent the same procedure as the experimental group. The mortality rate was consistent with the former experiment (20 %). There were no significant changes in serum ANP level in vitro and in vivo (within 48 and 24 h, respectively). But there was a significant decrease in serum ANP level at 48 h postmortem in vivo (P = 0.001). A female patient who expired due to neurogenic shock during a hysteroscopy was reported. Neither fatal primary disease nor evidence for mechanical injuries or intoxication was found according to the autopsy. The serum ANP level was assayed as a supplementary indicator and was found to be three-fold higher than the normal maximum limit. Combined with the animal experiment, this case highlights that serum ANP has the potential to be an objective indicator for the diagnosis of death due to neurogenic shock.

  18. Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

    PubMed

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei; Kangawa, Kenji

    2017-02-07

    Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

  19. Serum Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated with Low Left Ventricular Ejection Fraction and Elevated Plasma Brain-Type Natriuretic Peptide Level

    PubMed Central

    Fujita, Shu-ichi; Tanaka, Suguru; Maeda, Daichi; Morita, Hideaki; Fujisaka, Tomohiro; Takeda, Yoshihiro; Ito, Takahide; Ishizaka, Nobukazu

    2017-01-01

    Background Recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR), a biomarker of subclinical levels of inflammation, is significantly correlated with cardiovascular events. Purpose We investigated the association between suPAR and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and plasma B-type natriuretic peptide (BNP) among cardiac inpatients. Methods and Results In total, 242 patients (mean age 71.3 ± 9.8 years; 70 women) admitted to the cardiology department were enrolled in the study. suPAR was significantly correlated with LVEF (R = -0.24, P<0.001), LVMI (R = 0.16, P = 0.014) and BNP (R = 0.46, P<0.001). In logistic regression analysis, the highest suPAR tertile (> 3236 pg/mL) was associated with low LVEF (< 50%) and elevated BNP (> 300 pg/mL) with an odds ratio of 3.84 (95% confidence interval [CI], 1.22–12.1) and 5.36 (95% CI, 1.32–21.8), respectively, after adjusting for age, sex, log-transformed estimated glomerular filtration rate (log(eGFR)), C-reactive protein, and diuretic use. The association between suPAR and LVMI was not statistically significant. In multivariate receiver operating characteristic analysis, addition of log(suPAR) to the combination of age, sex, log(eGFR) and CRP incrementally improved the prediction of low LVEF (area under the curve [AUC], 0.827 to 0.852, P = 0.046) and BNP ≥ 300 pg/mL (AUC, 0.869 to 0.906; P = 0.029). Conclusions suPAR was associated with low LVEF and elevated BNP, but not with left ventricular hypertrophy, independent of CRP, renal function, and diuretic use among cardiac inpatients who were not undergoing chronic hemodialysis. PMID:28135310

  20. High Serum Levels of Pro-Brain Natriuretic Peptide (pro BNP) Identify Cardioembolic Origin in Undetermined Stroke

    PubMed Central

    Rodríguez-Yáñez, Manuel; Sobrino, Tomás; Blanco, Miguel; de la Ossa, Natalia Pérez; Brea, David; Rodríguez-González, Raquel; Leira, Rogelio; Dávalos, Antonio; Castillo, José

    2009-01-01

    Background: Stroke subtype diagnosis leads to specific therapies to reduce recurrences. Because nearly one third of patients remain with unknown etiology after a complete screening workup, we aim to investigate whether molecular markers of myocardial damage were associated with cardioembolic stroke and if they were useful to reclassify strokes of undetermined etiology. Methods: We included 262 patients with first ischemic stroke within the first 12 hours. Stroke subtype was evaluated by TOAST criteria. Stroke of undetermined origin were reclassified into likely atherothrombotic or likely cardioembolic according to a predefined non-validated algorithm. Blood samples were obtained on admission to determine serum levels of molecular markers (pro-BNP, pro-ANP and CK-MB) of myocardial damage. Results: Patients with cardioembolic infarct showed higher levels of pro-BNP, pro-ANP and CK-MB. Pro-BNP > 360 pg/mL was independently associated with cardioembolic stroke (OR: 28.51, CI95%: 5.90–136.75, p < 0.0001). Stroke etiology was undetermined in 82 patients (31%); 34 were reclassified as likely cardioembolic, 22 as likely atherothrombotic, and 26 remained as undetermined. Pro-BNP > 360 pg/mL was the only factor independently associated with likely cardioembolic stroke. Conclusions: Pro-BNP levels higher than 360 pg/mL are associated with cardioembolic stroke and may be useful to reclassify undetermined strokes as of cardioembolic origin. PMID:19729800

  1. Expression of natriuretic peptide receptor mRNA and functional response to atrial natriuretic peptide and C-type natriuretic peptide in rainbow trout (Oncorhynchus mykiss) head kidney leucocytes.

    PubMed

    Powell, M D; McWilliam, H; McLeod, J; Nankervis, S; Butler, R; Toop, T

    2008-04-01

    The stimulatory effect of vasomodulatory natriuretic peptide hormones on macrophages and peripheral blood leucocytes in mammals is well-established. However, the relationship in lower vertebrates has not been characterised. Expression of atrial natriuretic peptide, ventricular natriuretic peptide and C-type natriuretic peptide-1, and the guanylyl cyclase-linked (GC) natriuretic peptide receptor-A and -B-type receptors (NPR-A and NPR-B, respectively) was determined by PCR from the mRNA of rainbow trout head kidney leucocytes yielding gene fragments with 100% homology to the same respective natriuretic peptide and NPR-A and -B sequences obtained from other rainbow trout tissues. A mixed population of isolated rainbow trout head kidney leucocytes was stimulated in vitro with trout atrial natriuretic peptide (specific NPR-A agonist) and trout C-type natriuretic peptide (NPR-A and -B agonist) as well as the cGMP agonist 8-bromo-cGMP or the GC inhibitor 8-bromo-phenyl-eutheno-cGMP. Respiratory burst was stimulated by trout atrial natriuretic peptide, trout C-type natriuretic peptide-1 and 8-bromo-cGMP in a dose dependant manner with the highest activity as a result of stimulation with trout C-type natriuretic peptide-1 in excess of that achieved by phorbol myristate acetate (PMA). Equimolar concentrations of the inhibitor, inhibited the respiratory burst caused by the natriuretic peptides and 8-bromo-cGMP. The natriuretic peptide receptors on rainbow trout head kidney leucocytes appear to have a stimulatory function with regard to respiratory burst that is activated through a cGMP second messenger pathway and the natriuretic peptides expressed in the head kidney leucocytes may well act in a paracrine/autocrine manner.

  2. Pro-A-type natriuretic peptide and pro-adrenomedullin predict progression of chronic kidney disease: the MMKD Study.

    PubMed

    Dieplinger, Benjamin; Mueller, Thomas; Kollerits, Barbara; Struck, Joachim; Ritz, Eberhard; von Eckardstein, Arnold; Haltmayer, Meinhard; Kronenberg, Florian

    2009-02-01

    A-type natriuretic peptide (ANP) and adrenomedullin (ADM) are potent hypotensive, diuretic, and natriuretic peptides involved in maintaining cardiovascular and renal homeostasis. We conducted a prospective 7-year study of 177 nondiabetic patients with primary chronic kidney disease to see if ANP and ADM plasma concentrations predict the progression of their disease, using novel sandwich immunoassays covering the midregional epitopes of the stable prohormones (MRproANP and MR-proADM). Progression of chronic kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure, which occurred in 65 patients. Analysis of the receiver operating characteristic curve for the prediction of renal endpoints showed similar areas under the curve for the glomerular filtration rate (GFR) (0.838), MR-proANP (0.810), and MRproADM (0.876), respectively, as did the Kaplan-Meier curve analyses of the patients stratified according to the median of the respective markers. In separate multiple Cox-proportional hazard regression analyses, increased plasma concentrations of both peptides were each strongly predictive of the progression of chronic kidney disease after adjustments for age, gender, GFR, proteinuria and amino-terminal pro-B-type natriuretic peptide. Our study suggests that MR-proANP and MR-proADM are useful new markers of progression of primary nondiabetic chronic kidney disease.

  3. Increased extracellular water measured by bioimpedance and by increased serum levels of atrial natriuretic peptide in RA patients-signs of volume overload.

    PubMed

    Straub, Rainer H; Ehrenstein, Boris; Günther, Florian; Rauch, Luise; Trendafilova, Nadezhda; Boschiero, Dario; Grifka, Joachim; Fleck, Martin

    2016-04-26

    The aim of the study is to investigate water compartments in patients with rheumatoid arthritis (RA). Acute inflammatory episodes such as infection stimulate water retention, chiefly implemented by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism due to expected water loss (sweating etc.). Since SNS and HPA axis are activated in RA, inflammation might be accompanied by water retention. Using bioimpedance analysis, body composition was investigated in 429 controls and 156 treatment-naïve RA patients between January 2008 and December 2014. A group of 34 RA patients was tested before and after 10 days of intensified therapy. Levels of pro-atrial natriuretic peptide (proANP) and expression of atrial natriuretic peptide in synovial tissue were investigated in 15 controls and 14 RA patients. Extracellular water was higher in RA patients than controls (mean ± SEM: 49.5 ± 0.3 vs. 36.7 ± 0.1, % of total body water, p < 0.0001). Plasma levels of proANP were higher in RA than controls. RA patients expressed ANP in synovial tissue, but synovial fluid levels and synovial tissue superfusate levels were much lower than plasma levels indicating systemic origin. Systolic/diastolic blood pressure was higher in RA patients than controls. Extracellular water levels did not change in RA patients despite 10 days of intensified treatment. This study demonstrates signs of intravascular overload in RA patients. Short-term intensification of anti-inflammatory therapy induced no change of a longer-lasting imprinting of water retention indicating the requirement of additional treatment. The study can direct attention to the area of volume overload.

  4. Investigation of changes in brain natriuretic peptide serum levels and its diagnostic value in patients with mild and moderate head trauma, in patients referred to emergency department of Alzahra Hospital, Isfahan, 2013-2014

    PubMed Central

    Azizkhani, Reza; Keshavarz, Es’haq

    2016-01-01

    Background: Head trauma is one of the most common reasons for emergency department (ED) care. Over the past decade, initial management strategies in mild and moderate head trauma have become focused on selective computed tomography (CT) use based upon presence or absence of specific aspects of patient history and/or clinical examination which has received more attention following reports of increased cancer risk from CT scans. Recently changes in serum brain natriuretic peptide (BNP) levels following head trauma have been studied. We investigated the changes in serum levels of BNP in patients with mild and moderate head trauma, in whom the first brain CT scanning was normal. Materials and Methods: This study is a cross-sectional, descriptive research. It was performed in patients with mild and moderate head trauma. Forty-one patients with isolated mild and moderate traumatic brain injury (Glasgow Coma Scale = 9–15) were included. First brain CT scans were obtained during 2 h after ED arrival and the second one after 24 h. Plasma BNP levels were determined using a specific immunoassay system. Results: Twenty-three patients were in Group A (with normal first and second brain CT) and 18 patients in Group B (with normal first and abnormal second brain CT). With P = 0.001, serum BNP level = 9.04 was determined for differentiating two groups. Conclusion: We concluded that serum BNP level is higher in patients with mild and moderate head trauma with delayed pathologic changes in second brain CT relative to patients with mild and moderate head trauma and with normal delayed brain CT. PMID:28217629

  5. Natriuretic peptides buffer renin-dependent hypertension.

    PubMed

    Demerath, Theo; Staffel, Janina; Schreiber, Andrea; Valletta, Daniela; Schweda, Frank

    2014-06-15

    The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

  6. Plasma coenzyme Q10 concentration, antioxidant status, and serum N-terminal pro-brain natriuretic peptide concentration in dogs with various cardiovascular diseases and the effect of cardiac treatment on measured variables.

    PubMed

    Svete, Alenka Nemec; Verk, Barbara; Seliškar, Alenka; Tomsič, Katerina; Križman, Petra Jazbec; Petrič, Aleksandra Domanjko

    2017-04-01

    OBJECTIVE To determine the plasma total antioxidant capacity, erythrocyte superoxide dismutase activity, whole blood glutathione peroxidase activity, and plasma coenzyme Q10 (CoQ10) concentration in dogs with various stages of cardiovascular diseases and in healthy dogs; assess the influence of cardiac treatment on the levels of antioxidant variables, plasma CoQ10 concentration, and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, and determine any correlation between the disease severity (NT-proBNP concentration) and antioxidant variables or CoQ10 concentration. ANIMALS 43 dogs with various types and stages of cardiovascular diseases (congenital and acquired) and 29 healthy dogs. PROCEDURES Blood samples were collected from all dogs for spectrophotometric assessment of antioxidant variables. Plasma CoQ10 concentration was determined with a high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method. Serum NT-proBNP concentration was measured with an ELISA. RESULTS Values for antioxidant variables did not differ among groups of dogs with cardiovascular diseases, regardless of disease stage or treatment. Plasma CoQ10 concentration was significantly increased in treated dogs with congestive heart failure (CHF), compared with untreated patients. However, plasma CoQ10 concentration did not differ among heart failure classes. A significant, negative correlation between serum NT-proBNP and plasma CoQ10 concentrations was identified in treated CHF-affected dogs, suggesting that low plasma CoQ10 concentration may be associated with increased severity of CHF. CONCLUSIONS AND CLINICAL RELEVANCE The antioxidant variables evaluated were not altered in dogs with CHF, regardless of cardiac disease stage or treatment. Further investigation into the possible effects of CoQ10 supplementation in dogs with advanced stages of CHF is warranted.

  7. Natriuretic peptides and the heart: current and future implications for clinical biochemistry.

    PubMed

    Penney, M D

    2005-11-01

    The measurement of B-type natriuretic peptides in plasma is under intense promotion as a method of screening for heart failure. This article provides a historical context for this contention, and attempts to highlight what practical problems may be encountered in establishing a screening service from a clinical biochemistry standpoint. B-type natriuretic peptide measurements may also prove, in future, to have a significant role in the objective monitoring of treatment for heart failure, and to be a valuable prognostic indicator in patients suffering from acute coronary syndrome.

  8. Serum levels of N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) in twin pregnancy.

    PubMed

    Yamada, Takashi; Koyama, Takahiro; Furuta, Itsuko; Takeda, Masamitsu; Nishida, Ryutaro; Yamada, Takahiro; Morikawa, Mamoru; Minakami, Hisanori

    2013-01-16

    Twin pregnancy differs considerably from singleton pregnancy in many aspects and it is unknown how serum NT-proBNP level behaves in women with twin pregnancies. Serum NT-proBNP levels were determined longitudinally at gestational weeks (GW) 24 and 35 in normotensive women with 13 twin and 99 singleton pregnancies. The effects of maternal demographic characteristics on NT-proBNP levels were also analyzed. The serum NT-proBNP levels (pg/ml) in twin pregnancies, which were not different from those in singleton pregnancies at 24 GW (26±15 vs. 40±27, respectively, P=0.0718), increased significantly (P=0.0038) and were significantly higher than those in singleton pregnancies at 35 GW (72±49 vs. 34±24, P<0.0001). In the analysis including women with singleton pregnancies, the serum levels of NT-proBNP at 35 GW were significantly inversely correlated with pre-pregnancy body mass index (BMI, kg/m(2)) and were significantly higher in nulliparous than multiparous women. Thus, women with twin pregnancy were likely to exhibit an increase in serum NT-proBNP levels in the late stage of pregnancy, especially in lean and nulliparous women. The relative greater blood volume expansion occurring in twin than in singleton pregnancies was considered to be responsible for this phenomenon.

  9. The atrial natriuretic factor.

    PubMed Central

    Genest, J

    1986-01-01

    In less than three years since the rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats was reported the factor responsible for the diuretic, natriuretic, and vasodilating activity of the atrial homogenates was isolated, its chemical structure elucidated, and its total synthesis achieved. Also the cDNA and the gene encoding for the atrial natriuretic factor in mice, rats, and man have been cloned and the chromosomal site identified. The major effects of this hormone are vasodilatation, prevention and inhibition of the contraction induced by noradrenaline and angiotensin II, diuresis, and natriuresis associated in most instances with a pronounced increase in glomerular filtration rate and filtration fraction, inhibition of aldosterone secretion, and considerable stimulation of particulate guanylate cyclase activity. High density specific binding sites have been demonstrated in the zona glomerulosa of the adrenal cortex, in the renal glomeruli, and in the collecting ducts, and in the brain areas involved in the regulation of blood pressure and of sodium and water (AV3V region, subfornical organ, nucleus tractus solitarius, area postrema). Images Fig 1 Fig 5 PMID:2945572

  10. Genetic variation in the natriuretic peptide system and heart failure.

    PubMed

    Lanfear, David E

    2010-05-01

    Heart failure (HF) is a modern epidemic and is one of the few cardiovascular diseases which is increasing in prevalence. The growing importance of the Natriuretic Peptide (NP) system in HF is well recognized. Laboratory tests for B-type Natriuretic Peptide (BNP) have proven value as diagnostic and prognostic tools in HF and are now part of routine clinical care. Furthermore, recombinant atrial natriuretic peptide (ANP) (carperitide) and BNP (nesiritide) and are approved HF therapies in Japan and the US, respectively and additional natriuretic peptides (e.g., CNP, urodilatin, and designer NPs) are under investigation for use in HF. Common genetic sequence variants are increasingly being recognized as determinants of disease risk or drug response and may help explain a portion of the inter-individual variation in the human NP system. This review describes current knowledge of NP system genetic variation as it pertains to HF as well as ongoing studies and where the field is expected to progress in the near future. To briefly summarize, NP system genetic variants have been associated with alterations in gene expression, NP levels, and cardiovascular disease. The next step forward will include specific investigations into how this genetic variation can advance 'Personalized Medicine', such as whether they impact the utility of diagnostic BNP testing or effectiveness of therapeutic NP infusion. This is already in progress, with pharmacogenetic studies of nesiritide currently underway. We expect that within 5 years there should be a reasonable idea of whether NP system genetic variation will have important clinical implications.

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

    DTIC Science & Technology

    2009-08-25

    impedance (i.e., hypertension, increased TPR, aortic stenosis , etc.) will necessitate greater systolic ventricular pressure (3). Afterload is increased...ventricular pressure needed to eject blood in systole, can result from uncontrolled hypertension and/or reduced blood flow due to incomplete aortic valve...ventricular filling occurs because of conditions such as mitral 4 stenosis (narrowing of the mitral valve opening) and tamponade (fluid fills the

  12. Vascular effects and electrolyte homeostasis of the natriuretic peptide isolated from Crotalus oreganus abyssus (North American Grand Canyon rattlesnake) venom.

    PubMed

    Da Silva, S L; Dias-Junior, C A; Baldasso, P A; Damico, D C S; Carvalho, B M A; Garanto, A; Acosta, G; Oliveira, E; Albericio, F; Soares, A M; Marangoni, S; Resende, R R

    2012-08-01

    Crotalus oreganus abyssus is a rattlesnake that is usually found in the Grand Canyon, United States of America. Knowledge regarding the composition of C. o. abyssus venom is scarce. New natriuretic peptides (NPs) have been isolated and characterized from the venoms of members of the Crotalinae family. The NP family comprises three members, ANP (atrial natriuretic peptide), BNP (b-type natriuretic peptide) and CNP (c-type natriuretic peptide), and has an important role in blood pressure regulation and electrolyte homeostasis. The aim of the present study was to characterize a novel natriuretic-like peptide (Coa_NP2), isolated from C. o. abyssus venom. The Coa_NP2 presents an average molecular mass of 3419.88Da (theoretical average molecular mass 3418.94Da, monoisotopic molecular mass 3416.66Da and theoretical PI 7.78) and its amino acid sequence presents the loop region that is characteristic of natriuretic peptides. The peptide has 32 amino acids and its complete sequence is SYGISSGCFGLKLDRIGTMSGLGCWRLLQDSP. Coa_NP2 is a natriuretic peptide of the ANP/BNP-like family, since the carboxyterminal region of CNP has its own NP domain. We demonstrate, herein, that Coa_NP2 produces a dose-dependent decrease in mean arterial pressure in rats, followed by significant increases in concentrations of markers of nitric oxide formation measured in the plasma and vasorelaxation in a thoracic aortic ring bath. The structural and biological aspects confirm Coa_NP2 as a new natriuretic peptide, isolated from snake venom.

  13. Brain Natriuretic Peptide: It's Not About the Brain or Just Another Smart Polypeptide--It's About the Heart.

    PubMed

    Carella, Dominick M

    2015-01-01

    Brain natriuretic peptide (BNP) is a cardiac hormone with diuretic, natriuretic, and vasodilator properties. Measurement of plasma B-type natriuretic peptide concentrations is increasingly used to aid diagnosis, assess prognosis, and tailor treatment in adults with congestive heart failure. Recent studies suggest that the peptide is also useful in pediatric patients. The diagnostic role of plasma BNP in neonates admitted to the NICU has shown promise as an aid in diagnosis in neonates with signs of congenital heart disease; as a biomarker of bronchopulmonary dysplasia, patent ductus arteriosus, and persistent pulmonary hypertension of the newborn; a predictive biomarker of the response to indomethacin in preterm infants; and, more significantly, in acute heart failure.

  14. B-type stars in eclipsing binaries

    NASA Astrophysics Data System (ADS)

    Ratajczak, Milena; Pigulski, Andrzej

    2016-07-01

    B-type stars in eclipsing binary systems are unique astrophysical tools to test several aspects of stellar evolution. Such objects can be used e.g. to determine the masses of Beta Cephei variable stars, as well as help to place tighter constraints on the value of the convective core overshooting parameter α. Both precise photometry and high-resolution spectroscopy with high SNR are required to achieve these goals, but since many of the targets are bright enough, the challenge is fair. Following this assumption, we shall explain how we plan to examine both the aforementioned aspects of stellar evolution using observations of B-type stars obtained with a wide range of spectrographs, as well as BRITE-Constellation satellites.

  15. A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis

    SciTech Connect

    Colantonio, D.; Casale, R.; Mammarella, M.; Pasqualetti, P. ); Desiati, P.; De Michele, G. )

    1991-01-01

    The acute effects of ethanol on plasma atrial natriuretic peptide levels were investigated in 4 clinically healthy males, aged 24-26 years, consumed either 750 ml of water as a control study, or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 99.12{plus minus}15.10 mg/dl at 60 min. Plasma atrial natriuretic peptide levels were significantly higher in the alcohol study compared to the control study at each time point, and with a peak at 10 min. Atrial natriuretic peptide levels showed a positive significant correlation with plasma antidiuretic hormone in the control group, while no relationship was found between the two peptides in the alcohol study. Moreover, a significant correlation exists between plasma atrial natriuretic peptide levels and systolic arterial blood pressure, and heart rate, and between the variations in atrial natriuretic peptide values and the variations in plasma sodium, serum ethanol, and plasma osmolality in the alcohol study. Acute ethanol intake causes an increase in urinary volume, and a decrease in urinary potassium excretion and urinary osmolality, and no change in urinary sodium excretion.

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

    SciTech Connect

    Misono, K. S.; Philo, J. S.; Arakawa, T.; Ogata, C. M.; Qiu, Y.; Ogawa, H.; Young, H. S.

    2011-06-01

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

  17. Effects of natriuretic peptides on electrical conduction in the sinoatrial node and atrial myocardium of the heart.

    PubMed

    Azer, John; Hua, Rui; Krishnaswamy, Pooja S; Rose, Robert A

    2014-03-01

    Natriuretic peptides, including B-type and C-type natriuretic peptide (BNP and CNP), are powerful regulators of the cardiovascular system; however, their electrophysiological effects in the heart, particularly in the sinoatrial node (SAN), are incompletely understood. We have used high-resolution optical mapping to measure the effects of BNP and CNP, and the roles of natriuretic peptide receptors (NPR-A, NPR-B and NPR-C), on electrical conduction within the SAN and atrial myocardium. In basal conditions BNP and CNP (50-500 nm) increased conduction velocity (CV) within the SAN by ∼30% at the high dose and shifted the initial exit site superiorly. These effects sped conduction from the SAN to the surrounding atrial myocardium and were mediated by the NPR-A and NPR-B receptors. In the presence of isoproterenol (1 μm) the NPR-C receptor made a major contribution to the effects of BNP and CNP in the heart. In these conditions BNP, CNP and the NPR-C agonist cANF each decreased SAN CV and shifted the initial exit site inferiorly. The effects of cANF (30% reduction) were larger than BNP or CNP (∼15% reduction), indicating that BNP and CNP activate multiple natriuretic peptide receptors. In support of this, the inhibitory effects of BNP were absent in NPR-C knockout mice, where BNP instead elicited a further increase (∼25%) in CV. Measurements in externally paced atrial preparations demonstrate that the effects of natriuretic peptides on CV are partially independent of changes in cycle length. These data provide detailed novel insight into the complex effects of natriuretic peptides and their receptors on electrical conduction in the heart.

  18. Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males.

    PubMed

    Skov, Jeppe; Holst, Jens Juul; Gøtze, Jens Peter; Frøkiær, Jørgen; Christiansen, Jens Sandahl

    2014-01-01

    The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1-ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma proANP concentrations were measured by an automated mid-region-directed proANP immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular E170. Urine was collected for measurements of sodium excretion. Although GLP1 infusion increased the urinary sodium excretion markedly, there were no significant changes in either proANP or proBNP concentrations. When GLP1 infusion was stopped, sodium excretion declined rapidly. As proANP concentration reflects ANP secretion, our data could not confirm the existence of a GLP1-ANP axis in humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated exclusively via ANP.

  19. B-type natriuretic peptide and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the Folic Acid for Vascular Outcome Reduction in...

  20. Usefulness of serum bilirubin levels as a biomarker for long-term clinical outcomes after percutaneous coronary intervention.

    PubMed

    Kim, Hyun-Wook; Choi, Dong-Hyun; Lim, Leejin; Lee, Young-Min; Kang, Joon Tae; Chae, Seung Seok; Ki, Young-Jae; Song, Heesang; Koh, Young-Youp

    2015-11-01

    The aim of this study was to evaluate the prognostic value of serum total bilirubin on the development of adverse outcomes after percutaneous coronary intervention (PCI) besides high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP). Serum total bilirubin, hs-cTnT, and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. There were 21 events of cardiac death during a mean of 25.8 months of follow-up. When the serum total bilirubin cut-off level (median value) was set to 0.58 mg/dL using the receiver operating characteristic curve, the sensitivity was 95.2 % and the specificity was 51.0 % for differentiating between the group with cardiac death and the group without cardiac death. Kaplan-Meier analysis revealed that the lower serum total bilirubin group (<0.58 mg/dL) had a significantly higher cardiac death rate than the higher serum total bilirubin group (≥0.58 mg/dL) (10.4 vs. 0.6 %, log-rank: P = 0.0001). In conclusion, low serum total bilirubin is a predictive marker for cardiac death after PCI.

  1. IDENTIFICATION OF MAGNETITE IN B-TYPE ASTEROIDS

    SciTech Connect

    Yang Bin; Jewitt, David E-mail: jewitt@ucla.ed

    2010-09-15

    Spectrally blue (B-type) asteroids are rare, with the second discovered asteroid, Pallas, being the largest and most famous example. We conducted a focused, infrared spectroscopic survey of B-type asteroids to search for water-related features in these objects. Our results show that the negative optical spectral slope of some B-type asteroids is due to the presence of a broad absorption band centered near 1.0 {mu}m. The 1 {mu}m band can be matched in position and shape using magnetite (Fe{sub 3}O{sub 4}), which is an important indicator of past aqueous alteration in the parent body. Furthermore, our observations of B-type asteroid (335) Roberta in the 3 {mu}m region reveal an absorption feature centered at 2.9 {mu}m, which is consistent with the absorption due to phyllosilicates (another hydration product) observed in CI chondrites. The new observations suggest that at least some B-type asteroids are likely to have incorporated significant amounts of water ice and to have experienced intensive aqueous alteration.

  2. Natriuretic peptide-guided management in heart failure.

    PubMed

    Chioncel, Ovidiu; Collins, Sean P; Greene, Stephen J; Ambrosy, Andrew P; Vaduganathan, Muthiah; Macarie, Cezar; Butler, Javed; Gheorghiade, Mihai

    2016-08-01

    Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

  3. Clinical Value of Natriuretic Peptides in Predicting Time to Dialysis in Stage 4 and 5 Chronic Kidney Disease Patients

    PubMed Central

    Sundqvist, Sofia; Larson, Thomas; Cauliez, Bruno; Bauer, Fabrice; Dumont, Audrey; Le Roy, Frank; Hanoy, Mélanie; Fréguin-Bouilland, Caroline; Godin, Michel

    2016-01-01

    Background Anticipating the time to renal replacement therapy (RRT) in chronic kidney disease (CKD) patients is an important but challenging issue. Natriuretic peptides are biomarkers of ventricular dysfunction related to poor outcome in CKD. We comparatively investigated the value of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as prognostic markers for the risk of RRT in stage 4 and 5 CKD patients, and in foretelling all-cause mortality and major cardiovascular events within a 5-year follow-up period. Methods Baseline plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche) were measured at inclusion. Forty-three patients were followed-up during 5 years. Kaplan-Meier analysis, with log-rank testing and hazard ratios (HR), were calculated to evaluate survival without RRT, cardiovascular events or mortality. The independent prognostic value of the biomarkers was estimated in separate Cox multivariate analysis, including estimated glomerular filtration rate (eGFR), creatininemia and comorbidities. Results During the first 12-month follow-up period, 16 patients started RRT. NT-proBNP concentration was higher in patients who reached endpoint (3221 ng/L vs 777 ng/L, p = 0.02). NT-proBNP concentration > 1345 ng/L proved significant predictive value on survival analysis for cardiovascular events (p = 0.04) and dialysis within 60 months follow-up (p = 0.008). BNP concentration > 140 ng/L was an independent predictor of RRT after 12 months follow-up (p<0.005), and of significant predictive value for initiation of dialysis within 60 months follow-up. Conclusions Our results indicate a prognostic value for BNP and NT-proBNP in predicting RRT in stage 4 and 5 CKD patients, regarding both short- and long-term periods. NT-proBNP also proved a value in predicting cardiovascular events. Natriuretic peptides could be useful predictive biomarkers for therapeutic guidance in CKD. PMID:27548064

  4. Sex Differences of the Natriuretic Peptide Polymorphism Associated With Angiographic Coronary Atherosclerosis

    PubMed Central

    Li, Terry Y.; Tse, M. Yat; Pang, Stephen C.; McLellan, Catherine S.; King, Will D.; Johri, Amer M.

    2017-01-01

    Background Polymorphisms within natriuretic peptide (NP) genes have been associated with clinical outcomes for cardiovascular disease (CVD), but no previous study has compared the effect of these polymorphisms between men and women. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in key genes of the NP system and coronary angiographic outcomes, with the focus on the sexual dimorphism in the effects of these SNPs. Methods Patients undergoing clinically indicated coronary angiography (n = 513, 328 men and 185 women) were consented and genotyped for NPPA rs5065, NPPB rs198389 and NPR2 rs10758325. Patients were stratified into having normal coronaries, non-obstructive coronary artery disease (CAD) or obstructive CAD, based on the highest stenosis in any epicardial artery. Average luminal narrowing across all four arteries was derived to represent the overall atherosclerotic burden. Results The frequency of NPPB rs198389 AA genotype was significantly higher in women with obstructive CAD (P = 0.014). The same association was not observed in males. With respect to atherosclerotic burden, an association was found between the AA genotype and average luminal narrowing in women (P = 0.005), but not in men. Conclusions The current study identified an association between an SNP of the NPPB gene and coronary atherosclerotic burden through angiographic evidence in women but not in men. These results suggest that B-type natriuretic peptide (BNP) may have more important involvement in the development of CAD in women compared to men, and as such, genotyping of the NPPB gene may serve as a potential biomarker to identify women with high risk for CAD. PMID:28275418

  5. Plasma concentrations of adrenomedullin and atrial and brain natriuretic peptides in patients with adrenal pheochromocytoma.

    PubMed

    Hu, Wei; Shi, Lei; Zhou, Pang-Hu; Zhang, Xiao-Bin

    2015-11-01

    The present study aimed to evaluate any changes in the plasma concentrations of adrenomedullin (ADM), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with adrenal pheochromocytoma (PC). The plasma concentrations of the three peptides were measured in 45 healthy control individuals and 90 untreated patients with PC, who consisted of 20 normotensive patients, 30 borderline hypertensive patients and 40 hypertensive patients. After 4 weeks of effective antihypertensive therapy for hypertensive PC patients, the concentrations of ADM, ANP and BNP were measured again, and laparoscopic adrenalectomy was then performed for all PC patients with values that were measured 2 weeks later. The plasma concentrations of the three peptides were significantly increased in the borderline hypertensive and hypertensive patients compared with the concentrations in control individuals and normotensive patients. In addition, there were significant differences between the levels of ADM, ANP and BNP in the borderline and hypertensive groups. The plasma ADM concentration was not associated with the blood urea nitrogen levels, serum creatinine levels or glomerular filtration rate, but was correlated with the serum epinephrine, serum norepinephrine and urine vanillylmandelic acid levels. In addition, the ADM concentration was associated with the systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and plasma concentrations of ANP and BNP in the hypertensive patients with PC. After 4 weeks of antihypertensive treatment, the values of the three peptides in the hypertensive patients with PC were not significantly changed. As expected, the values in borderline and hypertensive groups were significantly decreased 2 weeks subsequent to surgery, whereas there were no significant changes in the normotensive group. ADM may participate, along with ANP and BNP, in the mechanisms that counteract further elevation

  6. Investigations of the Magnetic a and B Type Stars

    NASA Astrophysics Data System (ADS)

    Wade, Gregg Allan

    In an effort to explore further the mechanisms responsible for magnetism and chemical peculiarity in the early-type stars, I have constructed models of the magnetic fields of individual A and B type stars, studied the evolutionary dependence of magnetism in the Ap/Bp stars, undertaken the first systematic study of linear polarisation in the spectral lines of magnetic A and B type stars, and searched for magnetic fields in the photospheres of canonically non-magnetic upper-main sequence stars. I present detailed studies of 8 magnetic Ap, Bp and He-strong stars. For 7 of these objects (84 UMa, iota Cas, HD 115708, HD 184927, HD 200311, HD 81009, and HD 192678) new models of the surface magnetic field structure have been developed using longitudinal field, field modulus, and broadband linear polarisation measurements. These models represent a substantial contribution to the accumulated data regarding the surface magnetic fields of upper-main sequence stars. One object (HD 59435) is in fact a spectroscopic binary (SB2), the secondary component of which is a magnetic Ap star. A detailed study of the evolutionary state of the components and the mean magnetic field modulus variation of the secondary is presented. The results of this analysis are consistent with the suggestion by Hubrig & Mathys (1994) that magnetism (and perhaps chemical peculiarity) arise late in the evolution of A and B type stars. In order to test further this possibility, a more extensive study of the evolutionary states and magnetic fields of 10 magnetic Ap stars was undertaken. This study indicates that the magnetic stars are distributed across the entire width of the main sequence, a result inconsistent with the hypothesis of Hubrig & Mathys. I furthermore present investigations of the Zeeman circular and linear polarisation measured within stellar spectral lines. The MuSiCoS spectropolarimeter was used to conduct the first systematic, high signal-to-noise ratio observations of Zeeman linear

  7. Atrial natriuretic factor increases vascular permeability

    SciTech Connect

    Lockette, W.; Brennaman, B. )

    1990-12-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  8. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  9. Boron Abundances in A and B-type Stars

    NASA Technical Reports Server (NTRS)

    Lambert, David L.

    1997-01-01

    Boron abundances in A- and B-type stars may be a successful way to track evolutionary effects in these hot stars. The light elements - Li, Be, and B - are tracers of exposure to temperatures more moderate than those in which the H-burning CN-cycle operates. Thus, any exposure of surface stellar layers to deeper layers will affect these light element abundances. Li and Be are used in this role in investigations of evolutionary processes in cool stars, but are not observable in hotter stars. An investigation of boron, however, is possible through the B II 1362 A resonance line. We have gathered high resolution spectra from the IUE database of A- and B-type stars near 10 solar mass for which nitrogen abundances have been determined. The B II 1362 A line is blended throughout; the temperature range of this program, requiring spectrum syntheses to recover the boron abundances. For no star could we synthesize the 1362 A region using the meteoritic/solar boron abundance of log e (B) = 2.88; a lower boron abundance was necessary which may reflect evolutionary effects (e.g., mass loss or mixing near the main-sequence), the natal composition of the star forming regions, or a systematic error in the analyses (e.g., non-LTE effects). Regardless of the initial boron abundance, and despite the possibility of non-LTE effects, it seems clear that boron is severely depleted in some stars. It may be that the nitrogen and boron abundances are anticorrelated, as would be expected from mixing between the H-burning and outer stellar layers. If, as we suspect, a residue of boron is present in the A-type supergiants, we may exclude a scenario in which mixing occurs continuously between the surface and the deep layers operating the CN-cycle. Further exploitation of the B II 1362 A line as an indicator of the evolutionary status of A- and B-type stars will require a larger stellar sample to be observed with higher signal-to-noise as attainable with the Hubble Space Telescope.

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

    PubMed Central

    Tourki, Bochra; Matéo, Philippe; Morand, Jessica; Elayeb, Mohamed; Godin-Ribuot, Diane; Marrakchi, Naziha; Belaidi, Elise; Messadi, Erij

    2016-01-01

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

  11. Myocardial tissue Doppler echocardiography and N-terminal B-type natriuretic peptide (NT-proBNP) in diastolic and systolic heart failure

    PubMed Central

    Knebel, Fabian; Eddicks, Stephan; Schimke, Ingolf; Bierbaum, Michael; Schattke, Sebastian; Beling, Mark; Raab, Vanessa; Baumann, Gert; Borges, Adrian C

    2008-01-01

    Background The aim of this prospective study was to assess the diagnostic value of NT-proBNP and the concordance with Tissue Doppler Echocardiography (including strain and longitudinal displacement) in diastolic and systolic heart failure. Methods and results 137 consecutive clinically stable patients were included (42 healthy controls, 43 with diastolic heart failure, 52 with systolic heart failure). In diastolic heart failure, basal septal strain was reduced (-24.8 ± 8.1% vs. controls. -18.5 ± 5.3%, p < 0.0001). In all patients with preserved systolic function, septal basal longitudinal displacement was impaired in patients with increased left-ventricular filling pressures (E/E' < 8: 13.5 mm ± 3.3 mm vs. E/E' > 15: 8.5 mm ± 2.3 mm, p = 0.001) parallel to NT-proBNP elevation (E/E' < 8: 45.8 pg/ml, IQR: 172.5 pg/ml vs. E/E' > 15: 402.0 pg/ml, IQR: 1337.2 pg/ml; p = 0.0007). In ROC analysis, NT-proBNP could detect patients with reduced left ventricular systolic function (LVEF ≥ 55%) with a good diagnostic accuracy. However, the diagnostic accuracy of NT-proBNP to detect diastolic dysfunction was lower. Conclusion Subtle changes of longitudinal myocardial function begin in diastolic heart failure and are further increased in systolic heart failure. In patients with preserved LV function, a complex approach with the integration of multiple parameters including Tissue Doppler echocardiography and NT-proBNP is necessary to classify patients. PMID:18778476

  12. Values of using QTc and N-terminal fragment of B-type natriuretic peptide as markers for early detection of acute antipsychotic drugs-induced cardiotoxicity.

    PubMed

    Khalaf, Mohamed A M; Abdelrahman, Tarek M; Abbas, Mohamed F

    2011-03-01

    We aimed at studying the acute cardiotoxicity of the most commonly used antipsychotics in Egypt using QTc interval and NT-proBNP as markers for the early detection of such cases. Eighty-two admitted patients, at El-Minia PCC (period from 1-7-2005 to 30-6-2010), were classified into 3 groups: I: acute thioridazine overdose (n = 28), II: acute pimozide overdose (n = 23), and III: acute clozapine overdose (n = 31). Patients were investigated for NT-proBNP level and QTc on admission (day 0) and after 24 h (day 1). All the studied drugs had the ability to induce cardiotoxicity in the form of hypotension and dysrhythmias. Thioridazine and pimozide had potentially serious cardiotoxic effects than clozapine. NT-proBNP levels were elevated significantly in all groups on days 0 and 1 when compared with the reference value and a significant decrease in the same parameter on day 1 when compared with that of day 0 within the same group. QTc showed a significant prolongation in all studied groups on days 0 and 1, and there was a significant shortening of QTc on day 1 when compared with that of day 0 within the same group. A significant positive correlation of NT-proBNP level elevation with QTc prolongation was reported in all groups on days 0 and 1. Serious dysrhythmias were associated with QTc prolongation greater than 500 ms. And it was concluded that NT-proBNP, in adjunction with QTc measurement, may be a valuable and sensitive laboratory biomarker to predict cardiotoxicity of antipsychotic overdose. Larger multicenter studies are still needed to verify this possible relationship.

  13. Natriuretic peptides in cetaceans: identification, molecular characterization and changes in plasma concentration after landing.

    PubMed

    Naka, Tadaomi; Katsumata, Etsuko; Sasaki, Kazuki; Minamino, Naoto; Yoshioka, Motoi; Takei, Yoshio

    2007-06-01

    Dolphins are aquatic animals free from gravity, and this may have imposed significant changes in their cardiovascular status and its hormonal regulation compared with terrestrial animals. This study molecularly characterized two major cardiovascular hormones, atrial and B-type natriuretic peptides (ANP and BNP) and measured their changes in dolphin plasma concentrations in relation to the cardiovascular status of the animal. We initially identified ANP and BNP in three species of dolphins (Lagenorhynchus obliquidens, Phocoenoides dalli and Tursiops truncatus). ANP precursors are highly conserved in most mammals, but dolphin BNP precursors were more variable. In molecular phylogenetic analyses, dolphin ANP and BNP precursors grouped with those of artiodactyls, particularly to the camel peptides. The chromatographic characterization of tissue and plasma molecular forms using specific radioimmunoassays showed that the predominant ANP and BNP in the atrium are prohormone and mature peptide, respectively, whereas mature ANP and BNP are circulating in the dolphin blood. A mass spectrometric analysis showed that atrial BNP consists of 26 amino acids, rather than the 32-amino-acid form detected in other mammals. Finally, changes in plasma ANP and BNP concentrations were examined in captive bottlenose dolphins (Tursiops truncatus) after their pool was drained. Plasma ANP and BNP concentrations did not change after landing, unlike terrestrial mammals. Plasma angiotensin II and cortisol concentrations did not change either, showing minor stress after landing. Since landed dolphins show a different cardiovascular status on land than terrestrial mammals, plasma ANP and BNP concentrations seem to reflect the cardiovascular status characteristic of dolphins.

  14. Orbital inclinations of late B-type spectroscopic binaries

    NASA Astrophysics Data System (ADS)

    Guthrie, B. N. G.

    1986-05-01

    Information on the orbital inclinations j of late B-type spectroscopic binaries (SB's) with periods between 3 and 50 days is obtained from the masses M1 of their primary components, derived from uvby-beta photometry, and the values of M1 sin cubed j. The cumulative distribution of j for a fairly complete sample of double-lined binaries (SB2's) with Hg-Mn primaries is consistent with that expected for random orientations of the orbital planes. The period-eccentricity relations for Hg-Mn SB's and normal, sharp-lined SB's do not differ significantly. Subsynchronous rotators occur among the components of Hg-Mn SB's (e.g. HR266, Kappa-Cnc, HR 4072, Chi-Lup and 74 Aqr) and superficially normal SB's (e.g. 64Ori, HR 7338 and possibly HR 4892); the subsynchronous primary of HR 7338 is metal poor. The slow rotation of Hg-Mn stars is probably due to special initial conditions or to a substantial loss of angular momentum during contraction to the main sequence. The orbital periods of three of the SB2's with nonsynchronous Hg-Mn components (HR 266, AR Aur and 74 Aqr) are only about 4 days, and these systems may pose a difficulty for the hypothesis that the abundance anomalies are due to the separation of elements by diffusion in quiescent atmospheres.

  15. A new endogenous natriuretic factor: LLU-alpha.

    PubMed Central

    Wechter, W J; Kantoci, D; Murray, E D; D'Amico, D C; Jung, M E; Wang, W H

    1996-01-01

    For over three decades, renal physiology has sought a putative natriuretic hormone (third factor) that might control the body's pool of extracellular fluid, an important determinant in hypertension, congestive heart failure, and cirrhosis. In our search for this hormone, we have isolated several pure natriuretic factors from human uremic urine that would appear, alone or in combination, to mark a cluster of phenomena previously presumed to be that of a single "natriuretic hormone." This paper reports the purification, chemical structure, and total synthesis of the first of these compounds, LLU-alpha, which proved to be 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman, presumably a metabolite of gamma-tocopherol. Both natural LLU-alpha and synthetic material are identical (except for optical activity) with respect to structure and biological activity. It appears that the natriuretic activity of LLU-alpha is mediated by inhibition of the 70 pS K+ channel in the apical membrane of the thick ascending limb of the kidney. Images Fig. 5 PMID:8650209

  16. Serum Adiponectin and Cardiometabolic Risk in Patients with Acute Coronary Syndromes

    PubMed Central

    Oliveira, Gustavo Bernardes de Figueiredo; França, João Ítalo Dias; Piegas, Leopoldo Soares

    2013-01-01

    Background The adipose tissue is considered not only a storable energy source, but mainly an endocrine organ that secretes several cytokines. Adiponectin, a novel protein similar to collagen, has been found to be an adipocyte-specific cytokine and a promising cardiovascular risk marker. Objectives To evaluate the association between serum adiponectin levels and the risk for cardiovascular events in patients with acute coronary syndromes (ACS), as well as the correlations between adiponectin and metabolic, inflammatory, and myocardial biomarkers. Methods We recruited 114 patients with ACS and a mean 1.13-year follow-up to measure clinical outcomes. Clinical characteristics and biomarkers were compared according to adiponectin quartiles. Cox proportional hazard regression models with Firth's penalization were applied to assess the independent association between adiponectin and the subsequent risk for both primary (composite of cardiovascular death/non-fatal acute myocardial infarction (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular death/non-fatal AMI/non-fatal stroke/ rehospitalization requiring revascularization). Results There were significant direct correlations between adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and significant inverse correlations between adiponectin and waist circumference, body weight, body mass index, Homeostasis Model Assessment (HOMA) index, triglycerides, and insulin. Adiponectin was associated with higher risk for primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p = 0.01 and p = 0.02, respectively). Conclusion In ACS patients, serum adiponectin was an independent predictor of cardiovascular events. In addition to the anthropometric and metabolic correlations, there was a significant direct correlation between adiponectin and BNP. PMID:24029961

  17. C-type natriuretic peptide stimulates ovarian follicle development.

    PubMed

    Sato, Yorino; Cheng, Yuan; Kawamura, Kazuhiro; Takae, Seido; Hsueh, Aaron J W

    2012-07-01

    C-type natriuretic peptide (CNP) encoded by the NPPC (Natriuretic Peptide Precursor C) gene expressed in ovarian granulosa cells inhibits oocyte maturation by activating the natriuretic peptide receptor (NPR)B (NPRB) in cumulus cells. RT-PCR analyses indicated increased NPPC and NPRB expression during ovarian development and follicle growth, associated with increases in ovarian CNP peptides in mice. In cultured somatic cells from infantile ovaries and granulosa cells from prepubertal animals, treatment with CNP stimulated cGMP production. Also, treatment of cultured preantral follicles with CNP stimulated follicle growth whereas treatment of cultured ovarian explants from infantile mice with CNP, similar to FSH, increased ovarian weight gain that was associated with the development of primary and early secondary follicles to the late secondary stage. Of interest, treatment with FSH increased levels of NPPC, but not NPRB, transcripts in ovarian explants. In vivo studies further indicated that daily injections of infantile mice with CNP for 4 d promoted ovarian growth, allowing successful ovulation induction by gonadotropins. In prepubertal mice, CNP treatment alone also promoted early antral follicle growth to the preovulatory stage, leading to efficient ovulation induction by LH/human chorionic gonadotropin. Mature oocytes retrieved after CNP treatment could be fertilized in vitro and developed into blastocysts, allowing the delivery of viable offspring. Thus, CNP secreted by growing follicles is capable of stimulating preantral and antral follicle growth. In place of FSH, CNP treatment could provide an alternative therapy for female infertility.

  18. Development of a simple IgE-independent anaphylactic model using buckwheat antigen and B-type CpG oligodeoxynucleotide from Streptococcus thermophilus.

    PubMed

    Yamamoto, Yoshinari; Shigemori, Suguru; Nigar, Shireen; Oshiro, Kazushi; Wang, Yeqin; Sato, Takashi; Shimosato, Takeshi

    2016-05-01

    We developed a severe anaphylactic model in mice using buckwheat antigen and B-type CpG-oligodeoxynucleotides (CpG-ODNs) from Streptococcus thermophilus genome. In typical systemic anaphylaxis models, animals are challenged with large quantity of antigens via an intravenous (i.v.) route. Here, we showed a simple anaphylactic shock after challenge via intraperitoneal (i.p.) route. The i.p. method is simpler than i.v. administration and has a lower risk for failure. To generate this anaphylactic model, 5-week-old female BALB/c mice were first i.p. sensitized with buckwheat antigen mixed with B-type CpG-ODN. After 2 weeks, mice were challenged with antigen to induce anaphylactic shock, which was evaluated by scoring the severity symptoms and measuring serum levels of various proteins and splenic cell producing cytokines. Immunoglobulin (Ig)G2a production and interferon-γ positive cells were markedly increased in mice immunized with antigen mixed with B-type CpG-ODN, whereas serum IgE levels were decreased by B-type CpG-ODN. We also examined the effects of various ODNs (A, B and C-type CpG-ODNs) and antigens (buckwheat, α-casein, β-lactoglobulin and ovalbumin) on anaphylactic severity, and found that the combination of buckwheat and B-type CpG-ODN induced the most intense anaphylactic shock. This model is expected to contribute to the study of the prevention of anaphylactic shock.

  19. 77 FR 4043 - Scientific Information Request on the Use of Natriuretic Peptide Measurement in the Management of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... Natriuretic Peptide Measurement in the Management of Heart Failure AGENCY: Agency for Healthcare Research and... manufacturers of natriuretic peptide measurement assays. Scientific information is being solicited to inform our Comparative Effectiveness Review of Use of Natriuretic Peptide Measurement in the Management of Heart...

  20. Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine levels with alterations in arterial stiffness: The Framingham Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors. We ex...

  1. Atrial Natriuretic Peptide and Renal Dopaminergic System: A Positive Friendly Relationship?

    PubMed Central

    Choi, Marcelo Roberto; Rukavina Mikusic, Natalia Lucía; Kouyoumdzian, Nicolás Martín; Kravetz, María Cecilia; Fernández, Belisario Enrique

    2014-01-01

    Sodium metabolism by the kidney is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Renal dopamine plays a central role in this interactive network. The natriuretic hormones, such as the atrial natriuretic peptide, mediate some of their effects by affecting the renal dopaminergic system. Renal dopaminergic tonus can be modulated at different steps of dopamine metabolism (synthesis, uptake, release, catabolism, and receptor sensitization) which can be regulated by the atrial natriuretic peptide. At tubular level, dopamine and atrial natriuretic peptide act together in a concerted manner to promote sodium excretion, especially through the overinhibition of Na+, K+-ATPase activity. In this way, different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome or hypertension, are associated with impaired action of renal dopamine and/or atrial natriuretic peptide, or as a result of impaired interaction between these two natriuretic systems. The aim of this review is to update and comment on the most recent evidences demonstrating how the renal dopaminergic system interacts with atrial natriuretic peptide to control renal physiology and blood pressure through different regulatory pathways. PMID:25013796

  2. The evidence of production or activation of a natriuretic factor in the liver.

    PubMed

    Ivanov, Y I

    1979-01-01

    The natriuretic activity was measured with the aid of bioassay in blood flowing out from the brain, kidney and liver before and after the expansion of extracellular space in dogs. In another experiments in rats the volume natriuresis and the natriuretic activity in blood were measured in controls and in animals with carbon tetrachloride liver dystrophy and pharmacological stimulation (dehydrocholic acid, Ca pantothenate, cyanocobalamin) of liver functions. In dogs, the level of natriuretic activity in blood flowing out of the liver before and after the expansion of extracellular fluid volume was significantly higher than that in arterial blood. In contrast, the natriuretic activity was not found in the blood flowing out of the brain and the kidney. In rats the experimental dystrophy of the liver decreased the content of a natriuretic factor in blood plasma and the expansion of extracellular space did not produce any natriuretic effect as compared to control rats. After pharmacological stimulation of the liver by dehydrocholic acid, Ca pantothenate and cyanocobalamine the volume expansion led to a significant increase of the excretion of sodium by the kidney and to the increase of the content of a natriuretic factor in blood plasma as compared to control rats. These facts are considered to support the view that a natriuretic factor is either synthesized or activated by the liver.

  3. A Test in Context Critical Evaluation of Natriuretic Peptide Testing in Heart Failure

    PubMed Central

    Francis, Gary S.; Felker, G. Michael; Tang, W.H. Wilson

    2016-01-01

    Circulating natriuretic peptide measurements have been used extensively over the past 15 years to diagnose and monitor patients with heart failure. We are still learning how complex the dynamics of natriuretic peptides can be in the interpretation of test results in individual patients. Although natriuretic peptide measurements are widely used in practice, there are questions regarding why these peptides may not necessarily track with blood volume or invasive hemodynamic measurements in individual patients. Interpretation of natriuretic peptide measurements will depend on many factors, including special patient populations, obesity, renal function, the state of congestion or decongestion, and whether patients are receiving specific therapies. Natriuretic peptide measurements have clearly revolutionized clinical care for patients with heart failure, but further research should provide insights to help use these measurements to individualize patient care beyond the current guidelines. PMID:26796399

  4. Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

    PubMed Central

    Shenker, Y; Sider, R S; Ostafin, E A; Grekin, R J

    1985-01-01

    Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake. PMID:2932471

  5. Plasma cardiac natriuretic peptide determination as a screening test for the detection of patients with mild left ventricular impairment.

    PubMed Central

    Omland, T.; Aakvaag, A.; Vik-Mo, H.

    1996-01-01

    OBJECTIVE: To determine the usefulness of measuring the cardiac natriuretic peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide, as screening tests for identifying patients with mild left ventricular impairment. DESIGN: Cross-sectional evaluation of the diagnostic accuracy of the cardiac natriuretic peptides. SETTING: Cardiac catheterisation unit, Norwegian central hospital. PATIENTS: A consecutive series of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One hundred and twenty eight of these patients had a history of previous myocardial infarction. MAIN OUTCOME MEASURES: The presence of normal and impaired left ventricular function, as evaluated by logistic regression analysis and estimation of the area under the receiver operating characteristic (ROC) curve (an index of overall diagnostic accuracy). Ventricular function was assessed by the measurement of left ventricular end diastolic pressure and angiographically determined left ventricular ejection fraction. RESULTS: Logistic regression analysis showed that plasma brain natriuretic peptide was the best predictor of increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001), decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the combination of left ventricular ejection fraction < or = 45% and left ventricular end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC function for the detection of left ventricular dysfunction were 0.789 for brain natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N-terminal pro-atrial natriuretic factor. CONCLUSIONS: Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and

  6. Preparation, structure, and digestibility of crystalline A- and B-type aggregates from debranched waxy starches.

    PubMed

    Cai, Liming; Shi, Yong-Cheng

    2014-05-25

    Highly crystalline A- and B-type aggregates were prepared from short linear α-1,4 glucans generated from completely debranched waxy maize and waxy potato starches by manipulating the chain length and crystallization conditions including starch solids concentration and crystallization temperature. The A-type crystalline products were more resistant to enzyme digestion than the B-type crystalline products, and the digestibility of the A- and B-type allomorphs was not correlated with the size of the aggregates formed. Annealing increased the peak melting temperature of the B-type crystallites, making it similar to that of the A-type crystallites, but did not improve the enzyme resistance of the B-type crystalline products. The possible reason for these results was due to the compact morphology as well as the denser packing pattern of double helices in A-type crystallites. Our observations counter the fact that most B-type native starches are more enzyme-resistant than A-type native starches. Crystalline type per se does not seem to be the key factor that controls the digestibility of native starch granules; the resistance of native starches with a B-type X-ray diffraction pattern is probably attributed to the other structural features in starch granules.

  7. Natriuretic peptides for the detection of paroxysmal atrial fibrillation

    PubMed Central

    Seegers, Joachim; Zabel, Markus; Grüter, Timo; Ammermann, Antje; Weber-Krüger, Mark; Edelmann, Frank; Gelbrich, Götz; Binder, Lutz; Herrmann-Lingen, Christoph; Gröschel, Klaus; Hasenfuß, Gerd; Feltgen, Nicolas; Pieske, Burkert; Wachter, Rolf

    2015-01-01

    Background and purpose Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study. Methods Natriuretic peptide levels were analysed in two independent patient cohorts (162 patients with arterial hypertension or other cardiovascular risk factors and 82 patients with retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and BNP were measured before the start of a 7-day Holter monitoring period carefully screened for AT/AF. Results 244 patients were included; 16 had paroxysmal AT/AF. After excluding patients with a history of AT/AF (n=5), 14 patients had newly diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4; 178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9 (201.4; 277.1) versus 90.8 (42.3–141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0; 58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to 0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively. Conclusions NT-proBNP and BNP levels are elevated in patients with silent AT/AF as compared with sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic peptide level initiated Holter monitoring may be a useful strategy in prevention of stroke or systemic embolism. PMID:26288739

  8. Relationship between branching density and crystalline structure of A- and B-type maize mutant starches.

    PubMed

    Gérard, C; Planchot, V; Colonna, P; Bertoft, E

    2000-06-02

    Amylopectin from two double maize mutant starches of A-crystalline (wxdu) and B-crystalline type (aewx) was subjected successively to hydrolysis involving alpha and beta amylases, which isolated clusters and all branching zones of clusters (BZC). Enzymatic analysis together with ionic and size-exclusion chromatography revealed the structural features of the clusters and BZC and their role in starch crystallization. A-type clusters were larger (dp(n) > 80) and contained more (but shorter) chains than B-type clusters. The BZC of A-type starch was also larger, but with a shorter distance between the branching points than in B-type BZC. A-type clusters had a densely packed structure and B-type a poorly branched structure. Models for the structure of A- and B-type clusters are presented, and a hypothesis for the influence of cluster geometry on crystallization is proposed.

  9. Influence of storage conditions on in vitro stability of atrial natriuretic peptide and of anesthesia on plasma atrial natriuretic peptide concentration in cats.

    PubMed

    Heishima, Yasuhiro; Hori, Yasutomo; Chikazawa, Seishiro; Kanai, Kazutaka; Hoshi, Fumio; Itoh, Naoyuki

    2016-08-01

    OBJECTIVE To investigate the in vitro stability of atrial natriuretic peptide (ANP) in plasma samples under various storage conditions and the influence of anesthesia on plasma ANP concentration in cats. ANIMALS 1 cat with congestive heart failure and 5 healthy adult mixed-breed cats. PROCEDURES A plasma sample from the cat with heart failure was serially diluted, and dilutional parallelism of ANP concentration was evaluated. Plasma samples containing aprotinin or serum samples from the 5 healthy cats were kept at room temperature (27°C) for ≤ 12 hours. Plasma samples from the same healthy cats were stored at -70°, -20°, or 4°C for ≤ 14 days. Plasma samples were obtained from the healthy cats before and during isoflurane anesthesia. Plasma ANP concentrations were measured at a commercial laboratory by use of a human ANP chemiluminescence assay. RESULTS Intra- and interassay coefficients of variation were 1.5% and 2.5%, respectively, and dilutional parallelism was established. Although ANP concentration decreased by 82.4 ± 13.6% (mean ± SD) after sample storage for 12 hours at room temperature, this decrease was prevented by aprotinin. Plasma ANP concentrations were stable for 7 days at -20°C and for 14 days at -70°C. However, concentrations decreased markedly to 57.6 ± 6.9% at -20°C and to 18.0 ± 3.0% at 4°C after 14 days. Plasma ANP concentration decreased significantly in cats during anesthesia and was correlated with blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that aprotinin should be added routinely in preparation of plasma samples from cats for measurement of ANP concentration, and those samples, if stored, should be frozen immediately at ≤ -20°C. General anesthesia or systemic blood pressure may affect plasma ANP concentration in cats.

  10. Endothelial C-type natriuretic peptide maintains vascular homeostasis.

    PubMed

    Moyes, Amie J; Khambata, Rayomand S; Villar, Inmaculada; Bubb, Kristen J; Baliga, Reshma S; Lumsden, Natalie G; Xiao, Fang; Gane, Paul J; Rebstock, Anne-Sophie; Worthington, Roberta J; Simone, Michela I; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F; Djordjevic, Snezana; Caulfield, Mark J; MacAllister, Raymond J; Selwood, David L; Ahluwalia, Amrita; Hobbs, Adrian J

    2014-09-01

    The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor-C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders.

  11. Endothelial C-type natriuretic peptide maintains vascular homeostasis

    PubMed Central

    Moyes, Amie J.; Khambata, Rayomand S.; Villar, Inmaculada; Bubb, Kristen J.; Baliga, Reshma S.; Lumsden, Natalie G.; Xiao, Fang; Gane, Paul J.; Rebstock, Anne-Sophie; Worthington, Roberta J.; Simone, Michela I.; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F.; Djordjevic, Snezana; Caulfield, Mark J.; MacAllister, Raymond J.; Selwood, David L.; Ahluwalia, Amrita; Hobbs, Adrian J.

    2014-01-01

    The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor–C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders. PMID:25105365

  12. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    SciTech Connect

    Higuchi, K.; Hashiguchi, T.; Ohashi, M.; Takayanagi, R.; Haji, M.; Matsuo, H.; Nawata, H.

    1989-01-01

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of (/sup 125/I)-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

  13. Comparison of usefulness of tissue Doppler imaging versus brain natriuretic peptide for differentiation of constrictive pericardial disease from restrictive cardiomyopathy.

    PubMed

    Sengupta, Partho P; Krishnamoorthy, Vijay K; Abhayaratna, Walter P; Korinek, Josef; Belohlavek, Marek; Sundt, Thoralf M; Chandrasekaran, Krishnaswamy; Seward, James B; Tajik, A Jamil; Khandheria, Bijoy K

    2008-08-01

    Brain (B-type) natriuretic peptide (BNP) and tissue Doppler imaging may distinguish restrictive cardiomyopathy (RCMP) from idiopathic constrictive pericardial disease (CP). However, their comparative efficacy is unknown for patients with CP from secondary causes (e.g., surgery or radiotherapy). We compared the efficacy of tissue Doppler imaging and BNP for differentiation of RCMP (n = 15) and CP (n = 16) were compared. BNP was higher in patients with RCMP than CP (p = 0.008), but the groups overlapped, particularly for BNP <400 pg/ml. BNP was lower with idiopathic CP than secondary CP (139 +/- 50 vs 293 +/- 69 pg/ml; p <0.001) or RCMP (139 +/- 50 vs 595 +/- 499 pg/ml; p <0.001), but not significantly different between those with secondary CP and RCMP (293 +/- 69 vs 595 +/- 499 pg/ml; p = 0.1). Patients with CP and RCMP had less overlap in early diastolic and isovolumic contraction tissue Doppler imaging velocities compared with BNP, with clear separation of groups evident with mean early diastolic annular velocities (averaged from 4 walls). Early diastolic tissue Doppler imaging velocity was superior to BNP for differentiation of CP and RCMP (area under the curve 0.97 vs 0.76, respectively; p = 0.01). In conclusion, mean early diastolic mitral annular velocity correctly distinguished CP from RCMP even when there was a large overlap of BNP between the 2 groups.

  14. Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction.

    PubMed

    Nogi, Shinpei; Fujita, Shu-Ichi; Okamoto, Yusuke; Kizawa, Shun; Morita, Hideaki; Ito, Takahide; Sakane, Kazushi; Sohmiya, Koichi; Hoshiga, Masaaki; Ishizaka, Nobukazu

    2015-09-01

    Serum uric acid (SUA) is associated with the severity and prognosis of systolic heart failure. We investigated the potential association between SUA and cardiac diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men) who had preserved left ventricular ejection fraction. Presence of diastolic dysfunction was assessed by echocardiographic data, plasma B-type natriuretic peptide concentration, and left ventricular hypertrophy. Univariate analysis showed that the prevalence of diastolic dysfunction increased with increasing SUA value in women, but not in men. When sex-nonspecific SUA quartiles were used, multivariate logistic regression analysis, among female patients who were not taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and the fourth (SUA, ≥6.5 mg/dl) SUA quartiles were associated with diastolic dysfunction with an odds ratio of 3.25 (P < 0.05) and 8.06 (P < 0.001), respectively, when compared with the first SUA quartile (≤4.7 mg/dl). When sex-specific SUA quartiles were used among these population, multivariate logistic regression analysis showed that the fourth SUA quartile (≥5.7 mg/dl) was associated with diastolic dysfunction with an odds ratio of 5.34 (P < 0.05) when compared with the first SUA quartile (≤4.1 mg/dl). By contrast, the relationship between SUA and diastolic dysfunction was not significant in men, irrespective of which of the sex-nonspecific or sex-specific SUA quartiles were used. These data indicated that among cardiac patients with preserved ejection fraction, SUA was significantly associated with diastolic dysfunction in women but not in men.

  15. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

    PubMed

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-10-15

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

  16. Dehydration breakdown of antigorite and the formation of B-type olivine CPO

    NASA Astrophysics Data System (ADS)

    Nagaya, Takayoshi; Wallis, Simon R.; Kobayashi, Hiroaki; Michibayashi, Katsuyoshi; Mizukami, Tomoyuki; Seto, Yusuke; Miyake, Akira; Matsumoto, Megumi

    2014-02-01

    Peridotite formed by contact metamorphism and dehydration breakdown of an antigorite schist from the Happo area, central Japan shows a strong olivine crystallographic preferred orientation (Ol CPO). The lack of mesoscale deformation structures associated with the intrusion and the lack of microstructural evidence for plastic deformation of neoblastic grains suggest that olivine CPO in this area did not form as a result of solid-state deformation. Instead, the good correspondence between the original antigorite orientation and the orientation of the newly formed olivine implies the CPO formed by topotactic growth of the olivine after antigorite. Ol CPO is likely to develop by a similar process in subduction zone environments where foliated serpentinite is dragged down to depths where antigorite is no longer stable. The Happo Ol CPO has a strong a-axis concentration perpendicular to the lineation and within the foliation-commonly referred to as B-type Ol CPO. Seismic fast directions parallel to the ocean trench are observed in many convergent margins and are consistent with the presence of B-type Ol CPO in the mantle wedge of these regions. Experimental work has shown that B-type CPO can form by dislocation creep under hydrous conditions at relatively high stresses. There are, however, several discrepancies between the characteristics of natural and laboratory samples with B-type Ol CPO. (1) The formation conditions (stress and temperature) of some natural examples with B-type CPO fall outside those predicted by experiments. (2) In deformation experiments, slip in the crystallographic c-axis direction is important but has not been observed in natural examples of B-type CPO. (3) Experimental work suggests the presence of H2O and either high shear stress or relatively low temperatures are essential for the formation of B-type CPO. These conditions are most likely to be achieved close to subduction boundaries, but these regions are also associated with serpentinization

  17. Consensus document and recommendations on the use of natriuretic peptides in clinical practice.

    PubMed

    Pascual-Figal, D A; Casademont, J; Lobos, J M; Piñera, P; Bayés-Genis, A; Ordóñez-Llanos, J; González-Juanatey, J R

    2016-01-01

    Natriuretic peptides are a useful laboratory tool for the diagnosis, prognosis and treatment of patients with heart failure. Natriuretic peptides are used in various healthcare settings (consultations, emergency department, hospitalization, laboratory) and by various primary care and specialised professionals. However, their use in clinical practice is still scare and uneven. Properly using and interpreting natriuretic peptides in clinical practice requires a minimum of prelaboratory (pathophysiology), laboratory (methods) and postlaboratory (interpretation and integration of clinical data) expertise. The objective of this consensus document, developed by several scientific societies, is to update the necessary concepts and expertise on natriuretic peptides that enable its application in the diagnosis, prognosis and treatment of heart failure, in various healthcare environments.

  18. N-Terminal pro-brain natriuretic peptide levels in dichorionic diamniotic twins with selective intrauterine growth restriction.

    PubMed

    Fujioka, Kazumichi; Mizobuchi, Masami; Sakai, Hitomi; Iwatani, Sota; Wada, Keiko; Yoshimoto, Seiji; Nakao, Hideto

    2014-03-04

    Monochorionic diamniotic (MD) twins with selective intrauterine growth restriction (sIUGR) have known associations with cardiac complications. However, the cardiac load of dichorionic diamniotic (DD) twins with sIUGR (DD-sIUGR) remains unclear. N-terminal pro-brain natriuretic peptide (NT-pro BNP) is a convenient marker of cardiac dysfunction in neonates, and is elevated in MD twins with sIUGR (MD-sIUGR). However, there are no reports assessing serum NT-pro BNP levels in DD-sIUGR. Here, we aimed to clarify serum NT-pro BNP levels at birth in DD-sIUGR, and to compare them with those of MD-sIUGR. Forty-one DD twin pairs admitted to our center between October 2007 and January 2013 were enrolled in this study and separated into two groups: nine twins with sIUGR (DD-sIUGR group) and 32 twins without sIUGR (DD without sIUGR group). Sixteen MD twins with sIUGR (MD-sIUGR group) served as positive controls. Serum NT-pro BNP levels at birth in DD-sIUGR [median 2,115 pg/ml (range, 443-6,590 pg/ml)] were significantly higher than in DD without sIUGR [1,080 pg/ml (range, 313-3,470 pg/ml); p=0.001], and significantly lower than in MD twins with sIUGR [4,520 pg/ml (range, 529-62,400 pg/ml); p=0.04]. Serum NT-pro BNP levels between larger and smaller DD co-twins were significantly correlated (r = 0.582; p<0.0001). In conclusion, serum NT-pro BNP levels at birth in DD twins with sIUGR were higher than those without, and lower than in MD twins with sIUGR.

  19. The actions of atrial natriuretic factor on the vascular wall.

    PubMed

    Vlasuk, G P; Babilon, R W; Nutt, R F; Ciccarone, T M; Winquist, R J

    1987-08-01

    The actions of atrial natriuretic factor (ANF) on the vascular wall are diverse and show a profound regional heterogeneity. ANF is a potent relaxant of aortic smooth muscle, a response which is associated with activation of particulate guanylate cyclase and elevation in tissue levels of cyclic GMP. However, many large and small muscular arteries and most veins are unresponsive to the peptide. The regional vascular heterogeneity may be due to an altered distribution of high affinity receptors and (or) alterations in the coupling of receptor activation to elevations in cyclic 3',5'-guanosine monophosphate (cGMP). Species differences exist in the structural requirements for receptor activation as well as the effects of infused ANF on peripheral resistance. Although the relaxation to ANF in vitro does not require an intact endothelium, endothelial cells contain multiple receptor subtypes for ANF. Differences amongst tissues and (or) species in the receptor profile for ANF may, in part, explain some of heterogeneity in responsiveness to ANF.

  20. Atrial natriuretic factor in neonatal hypoxic-ischemic encephalopathy.

    PubMed

    Carbonell, X; Figueras, J; Salvia, M D; Esque, M T; Delgado, M P; Jimenez, R

    1993-01-01

    The influence of perinatal asphyxia in the secretion of atrial natriuretic factor (ANF) during the first 6 days of life, and its renal consequences are discussed. Comparison between 20 healthy term neonates and 19 with first--or second--degree hypoxic-ischemic encephalopathy (HIE) is made. Daily controls were performed on clinical and neurological examinations and administration of sodium and fluids. On the first and sixth days of life, 24 hours urine collection, natremia, natriuresis, fractionated excretion of sodium and creatinine clearance were determined. The ANF was performed at 1, 2, 3 and 6 days old, by R.I.A. The full term newborns with HIE showed a peak in ANF values on day two, as does the control group, thereafter maintaining higher levels, with a significant difference on day three and six. No correlation could be found between the ANF levels and the renal variables analyzed.

  1. Can Natriuretic Peptides be Used to Guide Therapy?

    PubMed Central

    Lupón, Josep; Jaffe, Allan S.

    2016-01-01

    Over the last 15 years, the hypothesis that intensified treatment directed at reducing natriuretic peptide (NP) concentrations may improve the outcomes of patients with heart failure (HF) has been scrutinized in several prospective clinical trials, with conflicting results. Collectively, however, the data suggest that NP concentrations may be useful in guiding HF management and improving HF-related morbidity and mortality. In this review, we summarize the existing data investigating the use of NPs as targets for outpatient HF therapy. We focus on the information gathered in randomized clinical trials and comprehensive meta-analyses, and also on the recommendations of international guidelines (primarily guidelines from the European Society of Cardiology and the American College of Cardiology/American Heart Association). Although the results for this approach are promising overall, additional well-designed prospective randomized controlled trials (e.g., the GUIDE-IT trial) are necessary to confirm or refute the utility of NP-guided outpatient HF management. PMID:27683534

  2. Amino acid sequence of atrial natriuretic peptides in human coronary sinus plasma.

    PubMed

    Yandle, T; Crozier, I; Nicholls, G; Espiner, E; Carne, A; Brennan, S

    1987-07-31

    Two atrial natriuretic peptides were purified from pooled human coronary sinus plasma by Sep-Pak extraction, immunoaffinity chromatography and reverse phase HPLC. The amino acid sequences of the two peptides were homologous with 99-126 human atrial natriuretic peptide (hANP) and 106-126 hANP, the latter being most probably linked to 99-105 ANP by the disulphide bond. The molar ratio of the peptides in plasma, as assessed by radioimmunoassay was 10:3.

  3. In-hospital brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide variations are predictors of short-term and long-term outcome in acute decompensated heart failure

    PubMed Central

    2011-01-01

    Acute decompensated heart failure is one of the most important causes of hospitalisation worldwide. Natriuretic peptides have shown their usefulness in the diagnosis and management of heart failure. Their variations during hospitalisation also appear useful to predict outcomes. In particular, data from the literature demonstrate that reduction from admission to discharge of brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide in these patients is a predictor of future cardiovascular events. PMID:21345261

  4. Human adrenal tumor cell line SW-13 contains a natriuretic peptide receptor system that responds preferentially to ANP among various natriuretic peptides

    SciTech Connect

    Mizuno, T.; Katafuchi, T.; Hagiwara, H.; Ito, T.; Kangawa, K.; Matsuo, H.; Hirose, S. )

    1990-12-31

    A new type of ANP receptor system which clearly distinguishes natriuretic peptides A and B (ANP and BNP) has been identified in the human adrenal tumor cell line SW-13 and characterized. SW-13 cells responded to nanomolar concentrations of ANP with large increases in cGMP levels but in the case of BNP, much higher concentrations were required to produce the same extent of response. This property is unique since the 140-kDa ANP receptors so far characterized do not discriminate between ANP and BNP. For comparison, various natriuretic peptide receptors were also re-characterized using the recently identified CNP.

  5. The effect of atrial natriuretic peptide infusion on intestinal injury in septic shock

    PubMed Central

    Elbaradey, Ghada F.; Elshmaa, Nagat Sayed; Hodeib, Hossam

    2016-01-01

    Background and Aims: The aim of this study is to assess the effect of atrial natriuretic peptide (ANP) on intestinal ischemia-reperfusion injury in septic shock. Material and Methods: A prospective randomized controlled, observer-blinded study was carried out in surgical Intensive Care Unit (ICU), University Hospital. Forty adult patients in septic shock were randomly divided into two groups, control group (Group C) received normal saline and ANP group (Group A) patients received ANP in the form of 1.5 mg vial added to 250 ml solvent in plastic bag (1 ml = 6 micg) given at 2 mcg/kg intravenous bolus over 1 min followed by 0.01 mcg/kg/min for 24 h. The primary outcome measurements were blood marker of intestinal hypoperfusion in form of intestinal fatty acid binding protein (I-FABP), malondialdehyde (MDA), myloperoxidase enzyme activity (MPO), protein carbonyl (PC), and glutathione peroxidase activity (GPA) measured before start of ANP infusion, 6 h, 12 h, and 24 h after start of infusion. The secondary outcome measurements were the duration of noradrenaline infusion, duration of ICU stay, hospital mortality rate, and complications related to ANP. Results: In comparison with Group C, Group A showed a significant decrease (P < 0.05) in serum level of MPO, MDA, PC, and I-FABP, with a significant increase (P < 0.05) in serum level of GPA, 6 h, 12 h, and 24 h after the start of ANP infusion. There was significant decrease (P < 0.05) in mean duration of noradrenaline infusion, the length of ICU stay and mortality rate in Group A in comparison with Group C. In Group A, seven patients had mean arterial blood pressure < 65 mmHg but respond to volume resuscitation, three patients serum sodium was 125–130 mmol/L. Conclusion: In cases of septic shock, concomitant administration of ANP with noradrenaline may have a protective effect against intestinal injury through a decrease in the level of intestinal hypoperfusion owing to its anti-inflammatory and antioxidant effect. PMID

  6. Brain Natriuretic Peptide Levels in Managing Pediatric Patients with Pulmonary Arterial Hypertension

    PubMed Central

    Bernus, Anna; Wagner, Brandie D.; Accurso, Frank; Doran, Aimee; Kaess, Heidi; Ivy, D. Dunbar

    2009-01-01

    Background Pulmonary arterial hypertension (PAH) is an important determinant of morbidity and mortality in children. In this study we aimed to investigate the value of Brain Natriuretic Peptide (BNP) in a cohort of children with PAH, with respect to monitoring disease severity as assessed by hemodynamic and echocardiographic parameters. Methods We performed a prospective study to determine if BNP varies over time in this population and if these changes track with hemodynamic or echocardiographic parameters. The population included a group of 78 pediatric patients from January 2005 until April 2008. All patients were diagnosed with PAH and had serum BNP, catheterization and echocardiographic variables collected longitudinally. Results The median BNP level, for all observations, was 36.0pg/ml (interquartile range [IQR], 18.0 to 76pg/ml). There was no strong correlation found between commonly used echocardiographic or hemodynamic data and BNP. However, using a bivariate model, the change in BNP measurements over time significantly correlated with the change in the hemodynamic and echocardiographic parameters. Patients with a BNP value greater than 180pg/ml had a decreased survival rate. Conclusions There is indication that BNP could be a useful marker to monitor disease severity in pediatric pulmonary hypertension. We show that simple correlations between variables and BNP are not likely to illustrate its usefulness due to variations in the normative levels. Instead, we propose that patient’s BNP levels should be monitored over time, as changes in BNP within a patient are likely to be more informative. PMID:18849405

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

    PubMed

    Mady, C; Fernandes, F; Ramires, F J A; Nastari, L; Buck, P C; Arteaga, E; Ianni, B M; Salemi, V M C

    2008-08-01

    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.

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

    PubMed

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

    2015-04-01

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

  9. A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

    PubMed

    Kamiya, Masataka; Sato, Naoki; Akiya, Mai; Okazaki, Hirotake; Takahashi, Yasuhiro; Mizuno, Kyoichi

    2013-01-01

    Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 μg/kg/minute, which did not control volume overload even at an increased dose of 0.025 μg/kg/minute. After a low dose of dopamine (DA) of 1.0 μg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

  10. Amino-terminal pro-brain natriuretic peptide in children with latent rheumatic heart disease

    PubMed Central

    Zachariah, Justin P; Aliku, Twalib; Scheel, Amy; Hasan, Babar S; Lwabi, Peter; Sable, Craig; Beaton, Andrea Z

    2016-01-01

    Background: Rheumatic heart disease (RHD) is a global cause of early heart failure. Early RHD is characterized by valvar regurgitation, leading to ventricular distention and possible elaboration of amino-terminal pro-brain natriuretic peptide (NT-proBNP). We investigated the ability of NT-proBNP to distinguish cases of latent RHD detected by echocardiographic screening from the controls. Materials and Methods: Ugandan children (N = 44, 36% males, mean age: 12 ± 2 years) with latent RHD (cases) and siblings (controls) by echocardiography were enrolled. Cases and controls were matched for age and sex, and they had normal hemoglobin (mean: 12.8 mg/dL). Children with congenital heart disease, pregnancy, left ventricular dilation or ejection fraction (EF) below 55%, or other acute or known chronic health conditions were excluded. RHD cases were defined by the World Heart Federation (WHF) 2012 consensus guideline criteria as definite. Controls had no echocardiography (echo) evidence for RHD. At the time of echo, venous blood samples were drawn and stored as serum. NT-proBNP levels were measured using sandwich immunoassay. Paired t-tests were used to compare NT-proBNP concentrations including sex-specific analyses. Results: The mean NT-proBNP concentration in the cases was 105.74 ± 67.21 pg/mL while in the controls, it was 86.63 ± 55.77 pg/mL. The cases did not differ from the controls (P = 0.3). In sex-specific analyses, male cases differed significantly from the controls (158.78 ± 68.82 versus 76 ± 42.43, P = 0.008). Female cases did not differ from the controls (75.44 ± 45.03 versus 92.30 ± 62.35 respectively, P = 0.4). Conclusion: Serum NT-proBNP did not distinguish between latent RHD cases and the controls. Sex and within-family exposures may confound this result. More investigation into biomarker-based RHD detection is warranted. PMID:27212845

  11. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

    PubMed

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-03-31

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

  12. Atrial natriuretic factor in maternal and fetal sheep

    SciTech Connect

    Cheung, C.Y.; Gibbs, D.M.; Brace, R.A.

    1987-02-01

    To determine atrial natriuretic factor (ANF) concentrations in the circulation and body fluids of adult pregnant sheep and their fetuses, pregnant ewes were anesthetized with pentobarbital sodium, and the fetuses were exteriorized for sampling. ANF concentration, as measured by radioimmunoassay, was 47 +/- 6 (SE) pg/ml in maternal plasma, which was significantly higher than the 15 +/- 3 pg/ml in maternal urine. In the fetus, plasma ANF concentration was 265 +/- 49 pg/ml, 5.6 times that in maternal plasma. No umbilical arterial and venous difference in ANF concentration was observed. Fetal urine ANF concentration was significantly lower than that in fetal plasma, and was similar to that measured in amniotic and allantoic fluid. In chronically catheterized maternal and fetal sheep, fetal plasma ANF was again 5.1 times that in maternal plasma, and these levels were not different from those measured in acutely anesthetized animals. These results demonstrate that immunoreactive ANF is present in the fetal circulation at levels higher than those found in the mother. The low concentration of ANF in fetal urine suggests that ANF is probably metabolized and/or reabsorbed by the fetal kidney.

  13. Brain natriuretic peptide predicts mortality in the elderly.

    PubMed Central

    Wallén, T.; Landahl, S.; Hedner, T.; Nakao, K.; Saito, Y.

    1997-01-01

    OBJECTIVE: To study whether prospective measurements of circulating concentrations of brain natriuretic peptide (BNP) could predict mortality in the general elderly population. DESIGN AND SETTING: Circulating BNP was measured in a cohort of 85 year olds from the general population who were followed up prospectively for five years as part of a longitudinal population study, "70 year old people in Gothenburg, Sweden". PATIENTS: 541 subjects from the 85 year old population in Gothenburg. All subjects were investigated for the presence or absence of cardiovascular disorder such as congestive heart failure, ischaemic heart disease, hypertension, and atrial fibrillation. Venous plasma samples were obtained for BNP analysis. MAIN OUTCOME MEASURE: Overall mortality during the prospective follow up period. RESULTS: Circulating concentrations of BNP predicted five-year mortality in the total population (P < 0.001). In subjects with a known cardiovascular disorder, five-year mortality was correlated with increased BNP concentrations (P < 0.01). Increased BNP concentrations predicted five-year mortality in subjects without a defined cardiovascular disorder (P < 0.05). CONCLUSIONS: In an elderly population, measurements of BNP may add valuable prognostic information and may be used to predict mortality in the total population as well as in patients with known cardiovascular disorders. In subjects without any known cardiovascular disorder, BNP was a strong and independent predictor of total mortality. PMID:9093047

  14. Atrial natriuretic factor binding sites in experimental congestive heart failure

    SciTech Connect

    Bianchi, C.; Thibault, G.; Wrobel-Konrad, E.; De Lean, A.; Genest, J.; Cantin, M. )

    1989-10-01

    A quantitative in vitro autoradiographic study was performed on the aorta, renal glomeruli, and adrenal cortex of cardiomyopathic hamsters in various stages of heart failure and correlated, in some instances, with in vivo autoradiography. The results indicate virtually no correlation between the degree of congestive heart failure and the density of 125I-labeled atrial natriuretic factor ((Ser99, Tyr126)ANF) binding sites (Bmax) in the tissues examined. Whereas the Bmax was increased in the thoracic aorta in moderate and severe heart failure, there were no significant changes in the zona glomerulosa. The renal glomeruli Bmax was lower in mild and moderate heart failure compared with control and severe heart failure. The proportion of ANF B- and C-receptors was also evaluated in sections of the aorta, adrenal, and kidney of control and cardiomyopathic hamsters with severe heart failure. (Arg102, Cys121)ANF (des-(Gln113, Ser114, Gly115, Leu116, Gly117) NH2) (C-ANF) at 10(-6) M displaced approximately 505 of (Ser99, Tyr126)125I-ANF bound in the aorta and renal glomeruli and approximately 20% in the adrenal zona glomerulosa in both series of animals. These results suggest that ANF may exert a buffering effect on the vasoconstriction of heart failure and to a certain extent may inhibit aldosterone secretion. The impairment of renal sodium excretion does not appear to be related to glomerular ANF binding sites at any stage of the disease.

  15. C-Type Natriuretic Peptide Analog as Therapy for Achondroplasia.

    PubMed

    Legeai-Mallet, Laurence

    2016-01-01

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

  16. Atrial natriuretic factor-like activity in rat posterior pituitary

    SciTech Connect

    Gutkowska, J.; Debinski, W.; Racz, K.; Thibault, G.; Garcia, R.; Kuchel, O.; Genest, J.; Cantin, M.

    1986-03-05

    The presence of a biologically active peptide: Atrial Natriuretic Factor (ANF) has been demonstrated in rat and human circulation and ANF is considered now as a new hormone. ANF may be involved in body fluid regulation. A very sensitive radioimmunoassay for rat ANF allowed the authors to search for immunoreactive ANF (IR-ANF) in rat posterior pituitary. Serial dilutions of homogenates of rat posterior pituitary showed a good parallelism with a reference curve in a radioimmunoassay system. The IR-ANF was extracted from rat posterior pituitary homogenates by activated Vycor glass beads. The lyophilized extract was purified by HPLC on C/sub 18/ ..mu.. Bondapak column. The HPLC yielded two IR-ANF peaks. Both isolated ANF-like material showed biological activity. The IR-ANF eluted with 33% acetonitrile, inhibited ACTH-stimulated aldosterone secretion with a similar potency as synthetic (Arg 101 - Tyr 126) ANF (0.7 x 10/sup -10/M). A much less potent ANF-like material was found in the second peak eluted with 36% acetonitrile. They conclude that ANF-like material is present in rat posterior pituitary and this suggest a possible role in ANF on AVP secretion directly in situ.

  17. Specific binding of atrial natriuretic factor in brain microvessels

    SciTech Connect

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-04-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

  18. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

    PubMed Central

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-01-01

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. PMID:25775533

  19. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

  20. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

  1. Clinical value of natriuretic peptides in chronic kidney disease.

    PubMed

    Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

    2015-01-01

    According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure.

  2. Diuretic and natriuretic activity of two mistletoe species in rats

    PubMed Central

    Jadhav, Namita; Patil, C. R.; Chaudhari, K. B.; Wagh, J. P.; Surana, S. J.; Jadhav, R. B.

    2010-01-01

    In different cultural groups, the hemiparasitic plants of the families Loranthaceae and Viscaceae (mistletoes) are frequently used in the treatment of hypertension and/or as diuretic agents. However, it remains unclear as to what commonality makes them diuretic agents or a remedy for hypertension. In this article, the diuretic activity of methanol extracts of Viscum articulatum (VA) Burm. f. and Helicanthus elastica (HE) (Ders.) Dans. in rats is reported. The extracts were administered orally at doses of 100, 200 and 400 mg/kg to rats that had been fasted and deprived of water for 18 hours. Investigations were carried out for diuretic, saluretic and natriuretic effects. The polyphenolic and triterpenoid contents were determined quantitatively using chemical assays and high performance liquid chromatography (HPLC) analysis, respectively. The extracts of VA and HE demonstrated significant and dose-dependent diuretic activity in rats. It was found that while VA mimics the furosemide pattern, HE demonstrated a dose-dependent increase in diuresis, along with an increase in potassium-sparing effects. Phytochemical analysis revealed that polyphenolics and triterpenoids, such as oleanolic acid and lupeol, are the major phytochemicals involved. It was also found that in different combinations, these phytochemicals differed in the way they influenced the electrolyte excretion. A higher content of polyphenolics in association with lower triterpenoid content was found to favor potassium-sparing effects. PMID:21808540

  3. Molecular cloning of natriuretic peptides from the heart of reptiles: loss of ANP in diapsid reptiles and birds.

    PubMed

    Trajanovska, Sofie; Donald, John A

    2008-04-01

    Atrial natriuretic peptide (ANP) and B-type NP (BNP) are hormones involved in homeostatic control of body fluid and cardiovascular regulation. Both ANP and BNP have been cloned from the heart of mammals, amphibians, and teleost fishes, while an additional cardiac peptide, ventricular NP, has been found in selected species of teleost fish. However, in chicken, BNP is the primary cardiac peptide identified thus far. In contrast, the types of NP/s present in the reptilian heart are unknown, representing a considerable gap in our understanding of NP evolution. In the present study, we cloned and sequenced a BNP cDNA from the atria of representative species of reptile, including crocodile, lizard, snake, and tortoise. In addition, we cloned BNP from the pigeon atria. The reptilian and pigeon BNP cDNAs had ATTTA repeats in the 3' untranslated region, as observed in all vertebrate BNP mRNAs. A high sequence homology was evident when comparing reptile and pigeon preproBNP with the previously identified chicken preproBNP. In particular, the predicted mature BNP-29 was identical between crocodile, tortoise, and chicken, with pigeon having a single amino acid substitution; lizard and snake BNP had seven and nine substitutions, respectively. Furthermore, an ANP cDNA could only be cloned from the tortoise atria. Since ANP was not isolated from the heart of any non-chelonian reptile and appears to be absent in birds, we propose that the ANP gene has been lost after branching of the turtles in the amniote line. This data provides new avenues for research on NP function in reptiles.

  4. Mouse B-Type Lamins Are Required for Proper Organogenesis But Not by Embryonic Stem Cells

    PubMed Central

    Kim, Youngjo; Sharov, Alexei A.; McDole, Katie; Cheng, Melody; Hao, Haiping; Fan, Chen-Ming; Gaiano, Nicholas; Ko, Minoru S. H.; Zheng, Yixian

    2012-01-01

    B-type lamins, the major components of the nuclear lamina, are believed to be essential for cell proliferation and survival. We found that mouse embryonic stem cells (ESCs) do not need any lamins for self-renewal and pluripotency. Although genome-wide lamin-B binding profiles correlate with reduced gene expression, such binding is not directly required for gene silencing in ESCs or trophectoderm cells. However, B-type lamins are required for proper organogenesis. Defects in spindle orientation in neural progenitor cells and migration of neurons probably cause brain disorganizations found in lamin-B null mice. Thus, our studies not only disprove several prevailing views of lamin-Bs but also establish a foundation for redefining the function of the nuclear lamina in the context of tissue building and homeostasis. PMID:22116031

  5. PROJECTED ROTATIONAL VELOCITIES OF 136 EARLY B-TYPE STARS IN THE OUTER GALACTIC DISK

    SciTech Connect

    Garmany, C. D.; Glaspey, J. W.; Bragança, G. A.; Daflon, S.; Fernandes, M. Borges; Cunha, K.; Oey, M. S.; Bensby, T.

    2015-08-15

    We have determined projected rotational velocities, v sin i, from Magellan/MIKE echelle spectra for a sample of 136 early B-type stars having large Galactocentric distances. The target selection was done independently of their possible membership in clusters, associations or field stars. We subsequently examined the literature and assigned each star as Field, Association, or Cluster. Our v sin i results are consistent with a difference in aggregate v sin i with stellar density. We fit bimodal Maxwellian distributions to the Field, Association, and Cluster subsamples representing sharp-lined and broad-lined components. The first two distributions, in particular, for the Field and Association are consistent with strong bimodality in v sin i. Radial velocities are also presented, which are useful for further studies of binarity in B-type stars, and we also identify a sample of possible new double-lined spectroscopic binaries. In addition, we find 18 candidate Be stars showing emission at Hα.

  6. Ventricular aneurysms complicating coxsackievirus group B, types 1 and 4 murine myocarditis.

    PubMed

    El-Khatib, M R; Chason, J L; Lerner, A M

    1979-02-01

    Suckling Swiss Webster mice were inoculated with 10(4)TCD50 of coxsackieviruses, group B types 1 or 4. Virulent necrotizing myocarditis resulted in 185 infected mice. Of the latter group, three (14.3%) nurslings on the 17th and 23rd day after inoculations had left ventricular aneurysms postmortem. None of 61 concurrently matched control mice developed aneurysms. Ventricular aneurysm is a suggested but previously undocumented complication of murine, and possibly human necrotizing transmural coxsackievirus myocarditis.

  7. An Einstein Observatory SAO-based catalog of B-type stars

    NASA Technical Reports Server (NTRS)

    Grillo, F.; Sciortino, S.; Micela, G.; Vaiana, G. S.; Harnden, F. R., Jr.

    1992-01-01

    About 4000 X-ray images obtained with the Einstein Observatory are used to measure the 0.16-4.0 keV emission from 1545 B-type SAO stars falling in the about 10 percent of the sky surveyed with the IPC. Seventy-four detected X-ray sources with B-type stars are identified, and it is estimated that no more than 15 can be misidentified. Upper limits to the X-ray emission of the remaining stars are presented. In addition to summarizing the X-ray measurements and giving other relevant optical data, the present extensive catalog discusses the reduction process and analyzes selection effects associated with both SAO catalog completeness and IPC target selection procedures. It is concluded that X-ray emission, at the level of Lx not less than 10 exp 30 ergs/s, is quite common in B stars of early spectral types (B0-B3), regardless of luminosity class, but that emission, at the same level, becomes less common, or nonexistent, in later B-type stars.

  8. Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies.

    PubMed

    Brasil, S; Richard, E; Jorge-Finnigan, A; Leal, F; Merinero, B; Banerjee, R; Desviat, L R; Ugarte, M; Pérez, B

    2015-06-01

    Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene, which codes for the enzyme adenosine triphosphate (ATP): cobalamin adenosyltransferase (ATR). This study reports differences in the metabolic and disease outcomes of two pairs of siblings with MMA cblB type, respectively harbouring the novel changes p.His183Leu/p.Arg190dup (P1 and P2) and the previously described mutations p.Ile96Thr/p.Ser174fs (P3 and P4). Expression analysis showed p.His183Leu and p.Arg190dup to be destabilizing mutations. Both were associated with reduced ATR stability and a shorter half-life than wild-type ATR. Analysis of several parameters related to oxidative stress and mitochondrial function showed an increase in reactive oxygen species (ROS) content, a decrease in mitochondrial respiration and changes in mitochondria morphology and structure in patient-derived fibroblasts compared to control cells. The impairment in energy production and the presence of oxidative stress and fission of the mitochondrial reticulum suggested mitochondrial dysfunction in cblB patients' fibroblasts. The recovery of mitochondrial function should be a goal in efforts to improve the clinical outcome of MMA cblB type.

  9. Expression of brain natriuretic peptide by human bone marrow stromal cells.

    PubMed

    Song, S; Kamath, S; Mosquera, D; Zigova, T; Sanberg, P; Vesely, D L; Sanchez-Ramos, J

    2004-01-01

    Bone marrow stromal cells (BMSC) have been shown to generate neural cells under experimental conditions in vitro and following transplantation into animal models of stroke and traumatic CNS injury. Hastened recovery from the neurological deficit has not correlated with structural repair of the lesion in the stroke model. Secretory functions of BMSC, such as the elaboration of growth factors and cytokines, have been hypothesized to play a role in the enhanced recovery of neurological function. Using gene expression arrays, real time RT-PCR and radioimmunoassay, we have found that brain natriuretic peptide (BNP) is synthesized and released by BMSC at physiologically relevant levels in vitro. BNP, like its close homolog atrial natriuretic peptide (ANP), exerts powerful natriuretic, diuretic and vasodilatory effects. We speculate that transplanted BMSCs facilitate recovery from brain and spinal cord lesions by releasing BNP and other vasoactive factors that reduce edema, decrease intracranial pressure and improve cerebral perfusion.

  10. Binding sites of atrial natriuretic peptide in tree shrew adrenal gland

    SciTech Connect

    Fuchs, E.; Shigematsu, K.; Saavedra, J.M.

    1986-09-01

    Adrenal gland binding sites for atrial natriuretic peptide-(99-126) (ANP) were quantitated in tree shrew (Tupaia belangeri) by incubation of adrenal sections with (3-(/sup 125/I)-iodotyrosyl28) atrial natriuretic peptide-(99-126), followed by autoradiography with computerized microdensitometry. In the adrenal glands, there are three types of ANP binding sites. One is located in the zona glomerulosa (BMax 84 +/- 6 fmol/mg protein; Kd 122 +/- 9 pM); the second in the zona fasciculata and reticularis (BMax 29 +/- 2 fmol/mg protein; Kd 153 +/- 6 pM) and the third in the adrenal medulla (BMax 179 +/- 1 fmol/mg protein; Kd 70 +/- 2 pM). Besides the influence of ANP on the regulation of adrenocortical mineralcorticoid and glucocorticoid secretion our findings raise the possibility for a local site of action of atrial natriuretic peptide in the regulation of adrenomedullary catecholamines in the tree shrew, primates and man.

  11. Natriuretic peptide receptor B signaling in the cardiovascular system: protection from cardiac hypertrophy.

    PubMed

    Pagel-Langenickel, Ines; Buttgereit, Jens; Bader, Michael; Langenickel, Thomas H

    2007-08-01

    Natriuretic peptides (NP) represent a family of structurally homologous but genetically distinct peptide hormones involved in regulation of fluid and electrolyte balance, blood pressure, fat metabolism, cell proliferation, and long bone growth. Recent work suggests a role for natriuretic peptide receptor B (NPR-B) signaling in regulation of cardiac growth by either a direct effect on cardiomyocytes or by modulation of other signaling pathways including the autonomic nervous system. The research links NPR-B for the first time to a cardiac phenotype in vivo and underlines the importance of the NP in the cardiovascular system. This manuscript will focus on the role of NPR-B and its ligand C-type natriuretic peptide in cardiovascular physiology and disease and will evaluate these new findings in the context of the known function of this receptor, with a perspective on how future research might further elucidate NPR-B function.

  12. Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease.

    PubMed

    Sharma, Abhishek; Ahmed, Vaseem; Garg, Aakash; Aggarwal, Chirag

    2015-01-01

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

  13. Natriuretic peptides modify Pseudomonas fluorescens cytotoxicity by regulating cyclic nucleotides and modifying LPS structure

    PubMed Central

    Veron, Wilfried; Orange, Nicole; Feuilloley, Marc GJ; Lesouhaitier, Olivier

    2008-01-01

    Background Nervous tissues express various communication molecules including natriuretic peptides, i.e. Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP). These molecules share structural similarities with cyclic antibacterial peptides. CNP and to a lesser extent BNP can modify the cytotoxicity of the opportunistic pathogen Pseudomonas aeruginosa. The psychrotrophic environmental species Pseudomonas fluorescens also binds to and kills neurons and glial cells, cell types that both produce natriuretic peptides. In the present study, we investigated the sensitivity of Pseudomonas fluorescens to natriuretic peptides and evaluated the distribution and variability of putative natriuretic peptide-dependent sensor systems in the Pseudomonas genus. Results Neither BNP nor CNP modified P. fluorescens MF37 growth or cultivability. However, pre-treatment of P. fluorescens MF37 with BNP or CNP provoked a decrease of the apoptotic effect of the bacterium on glial cells and an increase of its necrotic activity. By homology with eukaryotes, where natriuretic peptides act through receptors coupled to cyclases, we observed that cell-permeable stable analogues of cyclic AMP (dbcAMP) and cyclic GMP (8BcGMP) mimicked the effect of BNP and CNP on bacteria. Intra-bacterial concentrations of cAMP and cGMP were measured to study the involvement of bacterial cyclases in the regulation of P. fluorescens cytotoxicity by BNP or CNP. BNP provoked an increase (+49%) of the cAMP concentration in P. fluorescens, and CNP increased the intra-bacterial concentrations of cGMP (+136%). The effect of BNP and CNP on the virulence of P. fluorescens was independent of the potential of the bacteria to bind to glial cells. Conversely, LPS extracted from MF37 pre-treated with dbcAMP showed a higher necrotic activity than the LPS from untreated or 8BcGMP-pre-treated bacteria. Capillary electrophoresis analysis suggests that these different effects of the LPS may be due, at least in part, to

  14. Regulation of atrial natriuretic peptide receptors in the rat brain

    SciTech Connect

    Saavedra, J.M.

    1987-06-01

    We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99-126) in the rat brain. Quantitative autoradiographic techniques and a /sup 125/I-labeled ligand, /sup 125/I-ANP (99-126), were employed. After in vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with /sup 125/I-standards. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function.

  15. Functional atrial natriuretic peptide receptor in human adrenal tumor

    SciTech Connect

    Shionoiri, H.; Hirawa, N.; Takasaki, I.; Ishikawa, Y.; Oda, H.; Minamisawa, K.; Sugimoto, K.; Matsukawa, T.; Ueda, S.; Miyajima, E.

    1989-01-01

    The effects of synthetic human atrial natriuretic peptide (ANP) on the release of catecholamines, aldosterone, or cortisol were observed in human adrenal tumors obtained surgically from patients with pheochromocytoma, primary aldosteronism, or Cushing's syndrome, respectively. Each tumor tissue or adjacent normal cortical tissue was sectioned into slices, which were incubated in medium-199 in the presence or absence of adrenocorticotrophin (ACTH) and ANP. The amounts of epinephrine, norepinephrine, aldosterone, or cortisol released into the medium were measured. Existence of ANP receptors on the adrenal tissues was examined by binding assays, affinity labeling, and immunohistochemistry. Release of catecholamines from pheochromocytoma tissues was inhibited by ANP, and the presence of the ANP receptor on pheochromocytoma was further demonstrated by both binding assays and affinity labeling; Scatchard analysis revealed a single class of binding sites for ANP with a Kd of 1.0 nM and a Bmax of 0.4 pmol/mg of protein and the molecular size was estimated as 140 and a 70 kDa under nonreducing and reducing conditions, respectively. The presence of ANP receptors in pheochromocytoma was demonstrated by immunohistochemistry. ANP inhibited both basal and ACTH-stimulated aldosterone secretion in the slices of normal cortex, and localization of ANP receptors in zona glomerulosa cells was also demonstrated. However, ANP did not inhibit basal and ACTH-stimulated aldosterone and cortisol secretion in both tissue slices from aldosteronoma and Cushing's adenoma. Consistent with these observations, the absence of ANP receptors in adenoma tissues was determined by binding assays, affinity labeling, and immunohistochemistry.

  16. Weight Loss, Saline Loading, and the Natriuretic Peptide System

    PubMed Central

    Arora, Pankaj; Reingold, Jason; Baggish, Aaron; Guanaga, Derek P.; Wu, Connie; Ghorbani, Anahita; Song, Yanna; Chen‐Tournaux, Annabel; Khan, Abigail May; Tainsh, Laurel T.; Buys, Emmanuel S.; Williams, Jonathan S.; Heublein, Denise M.; Burnett, John C.; Semigran, Marc J.; Bloch, Kenneth D.; Scherrer‐Crosbie, Marielle; Newton‐Cheh, Christopher; Kaplan, Lee M.; Wang, Thomas J.

    2015-01-01

    Background In epidemiologic studies, obesity has been associated with reduced natriuretic peptide (NP) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading. Methods and Results We enrolled 15 obese individuals (mean BMI 45±5.4 kg/m2) undergoing gastric bypass surgery. Before and 6 months after surgery, subjects were admitted to the clinical research center and administered a large‐volume intravenous saline challenge. Echocardiography and serial blood sampling were performed. From the pre‐operative visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the 6‐month visit, N‐terminal pro‐atrial NP (Nt‐proANP) levels were 40% higher before, during, and after the saline infusion, compared with levels measured at the same time points during the pre‐operative visit (P<0.001). The rise in Nt‐pro‐ANP induced by the saline infusion (≈50%) was similar both before and after surgery (saline, P<0.001; interaction, P=0.2). Similar results were obtained for BNP and Nt‐proBNP; resting concentrations increased by 50% and 31%, respectively, after gastric bypass surgery. The increase in NP concentrations after surgery was accompanied by significant decreases in mean arterial pressure (P=0.004) and heart rate (P<0.001), and an increase in mitral annular diastolic velocity (P=0.02). Conclusion In obese individuals, weight loss is associated with a substantial increase in the “setpoint” of circulating NP concentrations. Higher NP concentrations could contribute to an enhanced ability to handle salt loads after weight loss. PMID:25595796

  17. Natriuretic peptides stimulate oocyte meiotic resumption in bovine.

    PubMed

    De Cesaro, Matheus P; Macedo, Mariana P; Santos, Joabel T; Rosa, Paulo R A; Ludke, Charles A; Rissi, Vitor B; Gasperin, Bernardo G; Gonçalves, Paulo B D

    2015-08-01

    The aim of the present study was to evaluate the expression of mRNA encoding natriuretic peptides (NPs) and their receptors in the cumulus-oocyte complex in cattle, a monovular mammalian species, and also to investigate the role of NPs in oocyte meiotic resumption in vitro. mRNA was observed for the NP precursor type-A (NPPA), type-C (NPPC), NP receptor-1 (NPR-1), receptor-2 (NPR-2) and receptor-3 (NPR-3) in bovine cumulus cells, and NPR-2 mRNA was observed in oocytes. These results are different from those obtained in mouse and pig models. The effects of NPPA, NP precursor type-B (NPPB) and NPPC on the resumption of arrested meiosis maintained by forskolin were studied at three different doses (10, 100 and 1000nM) with a 12h culture system. The germinal vesicle breakdown rates were greater (P≤0.05) in oocytes that were cultured in the presence of one or a combination of NPs (from 44% to 73%) than the negative control (from 24% to 27%). Additionally, it was demonstrated that the concentration of cyclic guanosine 3',5'-monophosphate (cGMP) is increased by NPPA and NPPC in oocytes and cumulus cells after 3h of in vitro maturation. However, in both groups, the concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in the oocyte did not increase between 3 and 6h of culture, even when forskolin was used. In summary, we observed the presence of mRNA for NPs and their receptors in the bovine cumulus-oocyte complex and demonstrated that, in vitro, NPPA, NPPB and NPPC stimulate oocyte meiotic resumption in a monovular species.

  18. Radioimmunoassay and characterization of atrial natriuretic peptide in human plasma

    SciTech Connect

    Yandle, T.G.; Espiner, E.A.; Nicholls, M.G.; Duff, H.

    1986-07-01

    A RIA for alpha-human atrial natriuretic peptide (alpha hANP) in plasma was developed and used to study the immunoreactive components secreted by the heart and circulating in peripheral venous plasma. The assay used (125I)diiodotyrosyl-alpha hANP, purified by high pressure liquid chromatography (HPLC), and a C-terminal-specific antiserum purchased from Peninsula Laboratories. Serial dilution curves of coronary sinus plasma samples were parallel with the standard curve, but significant nonparallelism was found in peripheral plasma samples of low immunoreactivity. When plasma was extracted using C-18 Sep-Pak cartridges, serial dilution curves from both coronary sinus and peripheral plasma samples were parallel to the standard curve. Although values for plasma samples assayed before and after extraction agreed closely (r = 0.99; n = 76), immunoreactive ANP in unextracted plasma was consistently greater (70-79 pmol/liter) than in extracts of plasma, suggesting non-specific interference by a component in plasma when assayed without extraction. Mean plasma immunoreactive ANP in 19 normal subjects consuming a normal salt intake was 14 +/- 1 (+/- SE) pmol/liter. In 5 normal men, increasing dietary sodium intake from 10 to 200 mmol sodium/day was associated with a 2-fold increment in ANP levels, and similar changes accompanied acute sodium loading using iv saline. Elevated values were found in patients with congestive heart failure (mean, 58 pmol/liter; range, 0-200; n = 9), chronic renal failure (mean, 118 pmol/liter; range, 30-290; n = 8), and primary aldosteronism (range, 32-90 pmol/liter; n = 3). HPLC and gel chromatographic analysis of the immunoreactive material found in coronary sinus plasma extracts showed that a large amount of the material eluted in the position of alpha hANP.

  19. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    PubMed Central

    Abdelalim, Essam M.; Bellier, Jean-Pierre; Tooyama, Ikuo

    2016-01-01

    Brain natriuretic peptide (BNP) exerts its functions through NP receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn (DH) of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and dorsal root ganglion (DRG). BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the DH of the spinal cord and in the neurons of the intermediate column (IC) and ventral horn (VH). Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I–II) labeled with calcitonin gene-related peptide (CGRP), suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase (ChAT) in the motor neurons of the VH. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NP receptor-A (NPR-A) and/or NP receptor-B (NPR-B) at the spinal cord level. PMID:27994541

  20. Changes of adrenomedullin and natriuretic peptides in patients with adrenal medullary hyperplasia prior to and following pharmacological therapy and adrenalectomy

    PubMed Central

    Zhou, Pang-Hu; Shi, Lei; Hu, Wei; Zhang, Xiao-Bin; Wang, Wei; Zhang, Li-Jun

    2016-01-01

    The aim of the present study was to investigate the pathophysiological functions of adrenomedullin (ADM), atrial and brain natriuretic peptides (ANP and BNP) in patients with adrenal medullary hyperplasia (AMH). Plasma ADM, ANP and BNP concentrations were measured in 20 patients with AMH, 35 patients with essential hypertension (EH), and 40 healthy control subjects. Following effective antihypertensive therapy, the values in AMH and EH patients were measured again and laparoscopic adrenalectomy was performed for AMH patients. At 2 weeks after surgery, the three peptides were measured again. The AMH patients had higher plasma concentrations of ADM, ANP and BNP compared with the EH and control subjects. There were significant differences in the values of ADM, ANP and BNP between adrenal vein and inferior vena cava and between AMH and contralateral adrenal vein. Plasma ADM concentration was correlated with serum epinephrine and norepinephrine and urine vanillylmandelic acid, in addition to systolic and diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and ANP and BNP values in the AMH group. Following antihypertensive treatment, ADM, ANP and BNP were significantly decreased in EH patients, but remained unchanged in AMH subjects. However, these concentrations significantly decreased following surgery. Therefore, the present results suggest that ADM, ANP and BNP may be involved in regulating adrenal medulla functions. PMID:27446289

  1. Pertussis toxin treatment does not block inhibition by atrial natriuretic factor of aldosterone secretion in cultured bovine zona glomerulosa cells

    SciTech Connect

    De Lean, A.; Cantin, M.

    1986-03-05

    The authors have previously reported that atrial natriuretic factor (ANF) potently inhibits PGE or forskolin-stimulation aldosterone secretion in bovine zona glomerulosa (ZG) by acting through specific high affinity receptors. In order to evaluate the functional role of the regulatory protein N/sub i/ and the inhibition of adenylate cyclase activity (AC) in ZG, the authors have studied the effect of treatment with PT on inhibition by ANF of aldosterone production. Primary cultures of ZG were treated for 18 hours in serum-free F12 medium with (0-100 ng/ml PT). No effect of PT pretreatment was observed either on basal, PGE-stimulated or ANF-inhibited levels of steroidogenesis. When membranes prepared from control ZG were ADP-ribosylated with (/sup 32/P) NAD in the presence of PT, two toxin-specific bands with 39 Kd and 41 Kd were documented on SDS gel. Cell pretreatment with as low as 1 ng/ml drastically reduced further labelling of these two bands while higher doses completely abolished them. Since PT treatment covalently modifies completely the toxin substrate without altering ANF inhibition of adrenal steroidogenesis, the authors conclude that N/sub i/ is not involved in the mode of action of ANF on aldosterone production.

  2. The B-type lamin is required for somatic repression of testis-specific gene clusters

    PubMed Central

    Shevelyov, Y. Y.; Lavrov, S. A.; Mikhaylova, L. M.; Nurminsky, I. D.; Kulathinal, R. J.; Egorova, K. S.; Rozovsky, Y. M.; Nurminsky, D. I.

    2009-01-01

    Large clusters of coexpressed tissue-specific genes are abundant on chromosomes of diverse species. The genes coordinately misexpressed in diverse diseases are also found in similar clusters, suggesting that evolutionarily conserved mechanisms regulate expression of large multigenic regions both in normal development and in its pathological disruptions. Studies on individual loci suggest that silent clusters of coregulated genes are embedded in repressed chromatin domains, often localized to the nuclear periphery. To test this model at the genome-wide scale, we studied transcriptional regulation of large testis-specific gene clusters in somatic tissues of Drosophila. These gene clusters showed a drastic paucity of known expressed transgene insertions, indicating that they indeed are embedded in repressed chromatin. Bioinformatics analysis suggested the major role for the B-type lamin, LamDmo, in repression of large testis-specific gene clusters, showing that in somatic cells as many as three-quarters of these clusters interact with LamDmo. Ablation of LamDmo by using mutants and RNAi led to detachment of testis-specific clusters from nuclear envelope and to their selective transcriptional up-regulation in somatic cells, thus providing the first direct evidence for involvement of the B-type lamin in tissue-specific gene repression. Finally, we found that transcriptional activation of the lamina-bound testis-specific gene cluster in male germ line is coupled with its translocation away from the nuclear envelope. Our studies, which directly link nuclear architecture with coordinated regulation of tissue-specific genes, advance understanding of the mechanisms underlying both normal cell differentiation and developmental disorders caused by lesions in the B-type lamins and interacting proteins. PMID:19218438

  3. C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling.

    PubMed

    Rose, R A; Hatano, N; Ohya, S; Imaizumi, Y; Giles, W R

    2007-04-01

    In the heart, fibroblasts play an essential role in the deposition of the extracellular matrix and they also secrete a number of hormonal factors. Although natriuretic peptides, including C-type natriuretic peptide (CNP) and brain natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the effects of CNP on fibroblast electrophysiology have not been examined. In this study, acutely isolated ventricular fibroblasts from the adult rat were used to measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non-selective cation current (NSCC). This current has a reversal potential near 0 mV. Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated NSCC was inhibited by the compounds Gd(3+), SKF 96365 and 2-aminoethoxydiphenyl borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts revealed the expression of several transient receptor potential (TRP) channel transcripts. Additional electrophysiological analysis showed that U73122, a phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are defining characteristics of specific TRPC channels. More detailed molecular analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5 transcripts. These data indicate that CNP, acting via the NPR-C receptor, activates a NSCC that is at least partially carried by TRPC channels in cardiac fibroblasts.

  4. MASS AND DENSITY OF THE B-TYPE ASTEROID (702) ALAUDA

    SciTech Connect

    Rojo, P.; Margot, J. L. E-mail: jlm@astro.ucla.edu

    2011-02-01

    Observations with the adaptive optics system on the Very Large Telescope reveal that the outer main belt asteroid (702) Alauda has a small satellite with primary to secondary diameter ratio of {approx}56. The secondary revolves around the primary in 4.9143 {+-} 0.007 days at a distance of 1227 {+-} 24 km, yielding a total system mass of (6.057 {+-} 0.36) x 10{sup 18} kg. Combined with an IRAS size measurement, our data yield a bulk density of 1570 {+-} 500 kg m{sup -3} for this B-type asteroid.

  5. Endogenous natriuretic factors 3: Isolation and characterization of human natriuretic factors LLU-{alpha}, LLU-{beta}{sub 1}, and LLU-{gamma}

    SciTech Connect

    Murray, E.D. Jr.; Kantoci, D.; DeWind, S.A.

    1995-12-31

    A low molecular weight endogenous substance believed to be responsible for extracellular fluid homeostasis in mammals has been sought for many years. Our goal is to isolate and structurally characterize this putative {open_quotes}natriuretic hormone{close_quotes}. We have developed an assay using the conscious rat to measure prolonged natriuresis, the activity originally described for this putative substance. Using this assay we have identified a number of natriuretic compounds isolated from human uremic urine. The collected urine is processed by ultrafiltration ({le} 3 kDa), gel filtration chromatography (G-25) and extraction with isopropanol and diethyl ether. The organic soluble material is then subjected to sequential high-performance liquid chromatography. We report here the initial characterization of two pure isolates (LLU-{alpha} and LLU-{gamma}) obtained by this method, and the structural elucidation of a third pure compound, LLU-{beta}{sub 1}, a natriuretic and previously unreported metabolite of the drug diltiazem. 33 refs., 7 figs., 4 tabs.

  6. Serum ferritin.

    PubMed

    Worwood, M

    1979-01-01

    (1) Brief introduction to iron metabolism and the biochemistry of ferritin. (2) Early studies of circulating ferritin. (3) Methods for measuring serum ferritin concentrations -- immunoradiometric, radioimmuno- and enzyme-linked immuno assays based on liver or spleen ferritin -- an evaluation of these techniques. (4) Serum ferritin concentrations in normal subjects -- definition of normality -- relationship between storage iron and serum ferritin concentrations -- changes during development from birth to old age -- iron deficiency -- variability of serum ferritin concentration -- evaluation of use of ferritin assay for assessment of storage iron levels. (5) Serum ferritin concentrations in disease -- hemochromatosis -- secondary iron overload -- liver damage -- infection and chronic disease -- cancer. (6) Assay of serum ferritin with antibodies to ferritins other than liver or spleen -- ferritinemia and cancer. (7) Properties of serum ferritin -- molecular weight -- iron content -- isoelectric focusing patterns -- carbohydrate content -- immunological properties. (8) Physiology of circulating ferritin -- release of ferritin from tissues -- origin of circulating ferritin -- clearance from the plasma -- iron and protein turnover. (9) Summary -- factors influencing serum ferritin concentrations and clinical use of ferritin estimations.

  7. Molecular cloning of natriuretic peptide receptor A from bullfrog (Rana catesbeiana) brain and its functional expression.

    PubMed

    Sekiguchi, T; Miyamoto, K; Mizutani, T; Yamada, K; Yazawa, T; Yoshino, M; Minegishi, T; Takei, Y; Kangawa, K; Minamino, N; Saito, Y; Kojima, M

    2001-08-08

    A comparative study of natriuretic peptide receptor (NPR) was performed by cloning the NPR-A receptor subtype from the bullfrog (Rana catesbeiana) brain and analyzing its functional expression. Like other mammalian NPR-A receptors, the bullfrog NPR-A receptor consists of an extracellular ligand binding domain, a hydrophobic transmembrane domain, a kinase-like domain and a guanylate cyclase domain. Sequence comparison among the bullfrog and mammalian receptors revealed a relatively low ( approximately 45%) similarity in the extracellular domain compared to a very high similarity ( approximately 92%) in the cytoplasmic regulatory and catalytic domains. Expression of NPR-A mRNA was detected in various bullfrog tissues including the brain, heart, lung, kidney and liver; highest levels were observed in lung. Functional expression of the receptor in COS-7 cells revealed that frog atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) elicited cyclic guanosine 3'5'-monophosphate production by stimulating the receptor in a dose-dependent manner from 10(-10) M concentrations. Rat ANP was also effective in stimulating the frog receptor whereas rat BNP and porcine BNP were less responsive to the receptor. On the other hand, frog C-type natriuretic peptide (CNP) as well as porcine CNP stimulated the receptor only at high concentrations (10(-7) M). This clearly indicates that the bullfrog receptor is a counterpart of mammalian NPR-A, and is specific for ANP or BNP but not for CNP.

  8. INTERACTING DISCIPLINES: Cardiac natriuretic peptides and obesity: perspectives from an endocrinologist and a cardiologist

    PubMed Central

    Ramos, Hugo R; Birkenfeld, Andreas L; de Bold, Adolfo J

    2015-01-01

    Since their discovery in 1981, the cardiac natriuretic peptides (cNP) atrial natriuretic peptide (also referred to as atrial natriuretic factor) and brain natriuretic peptide have been well characterised in terms of their renal and cardiovascular actions. In addition, it has been shown that cNP plasma levels are strong predictors of cardiovascular events and mortality in populations with no apparent heart disease as well as in patients with established cardiac pathology. cNP secretion from the heart is increased by humoral and mechanical stimuli. The clinical significance of cNP plasma levels has been shown to differ in obese and non-obese subjects. Recent lines of evidence suggest important metabolic effects of the cNP system, which has been shown to activate lipolysis, enhance lipid oxidation and mitochondrial respiration. Clinically, these properties lead to browning of white adipose tissue and to increased muscular oxidative capacity. In human association studies in patients without heart disease higher cNP concentrations were observed in lean, insulin-sensitive subjects. Highly elevated cNP levels are generally observed in patients with systolic heart failure or high blood pressure, while obese and type-2 diabetics display reduced cNP levels. Together, these observations suggest that the cNP system plays a role in the pathophysiology of metabolic vascular disease. Understanding this role should help define novel principles in the treatment of cardiometabolic disease. PMID:26115665

  9. Responses of Plasma Atrial Natriuretic Peptide to High Intensity Submaximal Exercise in the Heat,

    DTIC Science & Technology

    1987-06-01

    Natriuretic Peptide to LnHigh Intensity Submaximal Exercise in the Heat 0 " William J. Kraemer. Lawrence E. Armstrong, Roger W. Hubbard. :I[_] Louis J...atriopeptins in rat adrenal cells. Cir Res 57: 113-118. f V-0C -- V- - IF -I 7 - % 7 -. 17 Chartier L. Schiffrin EL. Thibault G (1984). Effects of atrial

  10. Diminished natriuretic response to dopamine D1 receptor agonist, SKF-38393 in obese Zucker rats.

    PubMed

    Marwaha, Aditi; Lokhandwala, Mustafa F

    2003-11-01

    Dopamine causes natriuresis and diuresis via activation of D1 receptors located on the renal proximal tubules and subsequent inhibition of the sodium transporters, Na-H exchanger and Na+/K+ ATPase. We have reported that dopamine fails to inhibit the activities of these two transporters in the obese Zucker rats (OZR). The present study was designed to examine the functional consequence of this phenomenon by determining the natriuretic and diuretic response to D1 receptor activation in lean Zucker rats (LZR) and OZR. In 11-12 week-old OZR and LZR, natriuretic and diuretic responses to intravenously administered D1 receptor agonist, SKF 38393 (3 microg/kg/min for 30 min) were measured under Inactin anesthesia. Plasma insulin and glucose levels were significantly higher in the obese rats as compared to the lean rats. Intravenous infusion of SKF 38393 caused significant increases in urine flow, urinary sodium excretion (U(Na)V), fractional excretion of sodium (FE(Na)), and glomerular filtration rate (GFR) in the lean rats. However, the natriuretic and diuretic response to SKF 38393 was markedly blunted in OZR. Infusion of SKF 38393 did not cause significant changes in the mean blood pressure and heart rate in either of the two groups. We suggest that the diminished natriuretic response to D1 receptor activation in OZR is the consequence of the previously reported defect in the D1 receptor-G-protein coupling and the failure of dopamine to inhibit the sodium transporters in these animals.

  11. Identification of a major QTL controlling the content of B-type starch granules in Aegilops

    PubMed Central

    Howard, Thomas; Rejab, Nur Ardiyana; Griffiths, Simon; Leigh, Fiona; Leverington-Waite, Michelle; Simmonds, James; Uauy, Cristobal; Trafford, Kay

    2011-01-01

    Starch within the endosperm of most species of the Triticeae has a unique bimodal granule morphology comprising large lenticular A-type granules and smaller near-spherical B-type granules. However, a few wild wheat species (Aegilops) are known to lack B-granules. Ae. peregrina and a synthetic tetraploid Aegilops with the same genome composition (SU) were found to differ in B-granule number. The synthetic tetraploid had normal A- and B-type starch granules whilst Ae. peregrina had only A-granules because the B-granules failed to initiate. A population segregating for B-granule number was generated by crossing these two accessions and was used to study the genetic basis of B-granule initiation. A combination of Bulked Segregant Analysis and QTL mapping identified a major QTL located on the short arm of chromosome 4S that accounted for 44.4% of the phenotypic variation. The lack of B-granules in polyploid Aegilops with diverse genomes suggests that the B-granule locus has been lost several times independently during the evolution of the Triticeae. It is proposed that the B-granule locus is susceptible to silencing during polyploidization and a model is presented to explain the observed data based on the assumption that the initiation of B-granules is controlled by a single major locus per haploid genome. PMID:21227932

  12. Comparison of physicochemical properties of B-type nontraditional starches from different sources.

    PubMed

    Huang, Jun; Zhao, Lingxiao; Man, Jianmin; Wang, Juan; Zhou, Weidong; Huai, Huyin; Wei, Cunxu

    2015-01-01

    Starches were isolated from rhizomes of Curcuma longa, Canna edulis and Canna indica and bulbs of Lilium lancifolium, and showed a B-type X-ray diffraction pattern. Their physicochemical properties were investigated and compared. These starches showed significantly different granule morphologies and sizes, but all had eccentric hila. The C. longa starch had the lowest content of amylopectin short branch-chain and branching degree and the highest content of amylopectin long branch-chain, and the L. lancifolium starch the highest content of amylopectin short branch-chain and branching degree and the lowest content of amylopectin long branch-chain among the four starches. The L. lancifolium starch had the lowest resistance to gelatinization, and showed the lowest pasting peak, hot and final viscosities, and the C. longa starch had the highest resistance to gelatinization, and showed the highest pasting hot, final and setback viscosities and the lowest pasting breakdown viscosity. The C. longa and L. lancifolium starches possessed very high and low resistance to hydrolysis and digestion, respectively. The above physicochemical properties would be useful for the applications of B-type starches in food and nonfood industries.

  13. Statistical imprints of CMB B-type polarization leakage in an incomplete sky survey analysis

    NASA Astrophysics Data System (ADS)

    Santos, Larissa; Wang, Kai; Hu, Yangrui; Fang, Wenjuan; Zhao, Wen

    2017-01-01

    One of the main goals of modern cosmology is to search for primordial gravitational waves by looking on their imprints in the B-type polarization in the cosmic microwave background radiation. However, this signal is contaminated by various sources, including cosmic weak lensing, foreground radiations, instrumental noises, as well as the E-to-B leakage caused by the partial sky surveys, which should be well understood to avoid the misinterpretation of the observed data. In this paper, we adopt the E/B decomposition method suggested by Smith in 2006, and study the imprints of E-to-B leakage residuals in the constructed B-type polarization maps, Script B(hat n), by employing various statistical tools. We find that the effects of E-to-B leakage are negligible for the Script B-mode power spectrum, as well as the skewness and kurtosis analyses of Script B-maps. However, if employing the morphological statistical tools, including Minkowski functionals and/or Betti numbers, we find the effect of leakage can be detected at very high confidence level, which shows that in the morphological analysis, the leakage can play a significant role as a contaminant for measuring the primordial B-mode signal and must be taken into account for a correct explanation of the data.

  14. Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility.

    PubMed

    Bézie, Y; Mesnard, L; Longrois, D; Samson, F; Perret, C; Mercadier, J J; Laurent, S

    1996-09-12

    We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10(-8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 x 10(-7) M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.

  15. Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure

    PubMed Central

    Testani, Jeffrey M.; Hanberg, Jennifer S.; Cheng, Susan; Rao, Veena; Onyebeke, Chukwuma; Laur, Olga; Kula, Alexander; Chen, Michael; Wilson, F. Perry; Darlington, Andrew; Bellumkonda, Lavanya; Jacoby, Daniel; Tang, W. H. Wilson; Parikh, Chirag R.

    2015-01-01

    Background Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure (ADHF) and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed. Methods and Results Based on well-established renal physiologic principles an equation was derived to predict net sodium output using a spot urine sample obtained one or two hours following loop diuretic administration. This equation was then prospectively validated in 50 ADHF patients using meticulously obtained timed 6-hour urine collections to quantitate loop diuretic induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2–4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91, p<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (AUC=0.95, 95% CI 0.89–1.0, p<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66, p<0.001) and lesser ability to predict poor natriuretic response (AUC=0.76, 95% CI 0.63–0.89, p=0.002). Conclusions In patients being treated for ADHF, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample. PMID:26721915

  16. Spectropolarimetry of B-type and C-type asteroids: Phase Curves and Wavelength Dependence

    NASA Astrophysics Data System (ADS)

    Maleszewski, C.; McMillan, R. S.; Smith, P. S.

    2014-12-01

    We present recent spectropolarimetric observations of eleven B- and C-type asteroids using SPOL (http://james.as.arizona.edu/~psmith/SPOL/) at the 2.3-m Bok and 1.6-m Kuiper telescopes. Our primary goal is to further constrain our understanding of the wavelength dependence of linear polarization. For each object, we produced polarimetric phase curves (linear polarization vs. phase angle) and measure the wavelength dependence in each observation by calculating the slope of each polarization spectrum. Previous analysis by Belskaya et al. (2009) shows that the slope of the polarization spectrum increases as the wavelength increases. No analysis of the wavelength dependence in B-types has occurred previously to our knowledge. For the five C-type (3 Ch- and 2 C-) objects observed, those of the Ch-type have larger minimum polarizations than of the C- subtype. This is consistent with polarimetric phase curves of similar asteroids by Gil-Hutton and Cañada-Assandri (2012). With respect to the wavelength dependence, our observed targets show an increase in polarization slope with wavelength, confirming the Belskaya (2009) result. After dividing the data by group, C- subtype objects have relatively flat polarization spectra, as opposed to the Ch- subtypes that have more rapidly changing slopes as phase angle increases. A mineralogical basis for the variety of wavelength dependences observed is most likely. Additional observations of the other C- subtypes will aid to distinguish how mineralogical variation affects polarization. It may also explain the wide range of polarization slopes measured near a phase angle of ten degrees in the Belskaya (2009) analysis. Six B-type asteroids were observed in a similar manner. As with the C-types, the polarimetric phase curves vary in shape, suggesting differences in albedo. Also, the wavelength dependence increases with wavelength, as shown for the C-types. On the other hand, all of the B-type objects have a similar wavelength dependence

  17. Cellular immune mechanisms in Coxsackievirus group B, type 3 induced myocarditis in Balb/C mice

    SciTech Connect

    Huber, S.A.; Job, L.P.

    1983-01-01

    Coxsackie B viruses are a common cause of viral myocarditis in humans. A murine model of the human disease has been developed using Coxsackievirus group B, type 3 and inbred Balb/c mice. Infection of T lymphocyte deficient mice does not result in significant myocarditis indicating the importance of T cells in this disease. The virus can be isolated from the hearts of T cell deficient and normal mice in equal concentrations. Virus elimination presumably is mediated by virus specific neutralizing antibody induced in both groups. T lymphocytes, natural killer cells and macrophage obtained from normal virus infected mice are all capable of lysing myofibers in vitro. Maximum lysis is obtained with the cytolytic T cells. When these cell populations or Coxsackievirus immune antibody were adoptively transferred into T lymphocyte deficient animals infected with the virus, only animals given T cells developed significant myocarditis.

  18. Spectral classification with the International Ultraviolet Explorer: An atlas of B-type spectra

    NASA Technical Reports Server (NTRS)

    Rountree, Janet; Sonneborn, George

    1993-01-01

    New criteria for the spectral classification of B stars in the ultraviolet show that photospheric absorption lines in the 1200-1900A wavelength region can be used to classify the spectra of B-type dwarfs, subgiants, and giants on a 2-D system consistent with the optical MK system. This atlas illustrates a large number of such spectra at the scale used for classification. These spectra provide a dense matrix of standard stars, and also show the effects of rapid stellar rotation and stellar winds on the spectra and their classification. The observational material consists of high-dispersion spectra from the International Ultraviolet Explorer archives, resampled to a resolution of 0.25 A, uniformly normalized, and plotted at 10 A/cm. The atlas should be useful for the classification of other IUE high-dispersion spectra, especially for stars that have not been observed in the optical.

  19. The Results of SED Simulations for a Young B-Type Star IRAS 22150+6109

    NASA Astrophysics Data System (ADS)

    Zakhozhay, O. V.; Miroshnichenko, A. S.; Kuratov, K. S.; Zakhozhay, V. A.; Khokhlov, S. A.; Zharikov, S. V.; Manset, N.

    2017-02-01

    We present the results of a spectroscopic analysis and spectral energy distribution (SED) modeling for a young B-type star IRAS 22150+6109. The optical multicolor photometric data were obtained at the Tien-Shan Astronomical Observatory near Almaty, Kazakhstan. Infrared photometry was taken from various sky surveys, such as IRAS, WISE, and AKARI. High-resolution optical spectra were obtained at the 3.6 m Canada-France-Hawaii Telescope (CFHT) and the 2.1 m telescope of the Observatorio Astronómico Nacional San Pedro Martir (OAN SPM). Fundamental parameters of the star are estimated under an assumption that it has a zero-age main-sequence luminosity and a spectral type of B3. The best fit to the SED implies that a large disk is located very far from the star (136 AU) and extended to 850 AU.

  20. Pharmacological chaperones as a potential therapeutic option in methylmalonic aciduria cblB type

    PubMed Central

    Jorge-Finnigan, Ana; Brasil, Sandra; Underhaug, Jarl; Ruíz-Sala, Pedro; Merinero, Begoña; Banerjee, Ruma; Desviat, Lourdes R.; Ugarte, Magdalena; Martinez, Aurora; Pérez, Belén

    2013-01-01

    Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene. This encodes the enzyme ATP:cob(I)alamin adenosyltransferase (ATR), which converts reduced cob(I)alamin to an active adenosylcobalamin cofactor. We recently reported the presence of destabilizing pathogenic mutations that retain some residual ATR activity. The aim of the present study was to seek pharmacological chaperones as a tailored therapy for stabilizing the ATR protein. High-throughput ligand screening of over 2000 compounds was performed; six were found to enhance the thermal stability of purified recombinant ATR. Further studies using a well-established bacterial system in which the recombinant ATR protein was expressed in the presence of these six compounds, showed them all to increase the stability of the wild-type ATR and the p.Ile96Thr mutant proteins. Compound V (N-{[(4-chlorophenyl)carbamothioyl]amino}-2-phenylacetamide) significantly increased this stability and did not act as an inhibitor of the purified protein. Importantly, compound V increased the activity of ATR in patient-derived fibroblasts harboring the destabilizing p.Ile96Thr mutation in a hemizygous state to within control range. When cobalamin was coadministrated with compound V, mutant ATR activity further improved. Oral administration of low doses of compound V to C57BL/6J mice for 12 days, led to increase in steady-state levels of ATR protein in liver and brain (disease-relevant organs). These results hold promise for the clinical use of pharmacological chaperones in MMA cblB type patients harboring chaperone-responsive mutations. PMID:23674520

  1. The Lyman-Continuum Fluxes and Stellar Parameters of O and Early B-Type Stars

    NASA Technical Reports Server (NTRS)

    Vacca, William D.; Garmany, Catherine D.; Shull, J. Michael

    1996-01-01

    Using the results of the most recent stellar atmosphere models applied to a sample of hot stars, we construct calibrations of effective temperature (T(sub eff)), and gravity (log(sub g)) with a spectral type and luminosity class for Galactic 0-type and early B-type stars. From the model results we also derive an empirical relation between the bolometric correction and T(sub eff) and log g. Using a sample of stars with known distances located in OB associations in the Galaxy and the Large Magellanic Cloud, we derive a new calibration of M(sub v) with spectral class. With these new calibrations and the stellar atmosphere models of Kurucz, we calculate the physical parameters and ionizing photon luminosities in the H(0) and He(0) continua for O and early B-type stars. We find substantial differences between our values of the Lyman- continuum luminosity and those reported in the literature. We also discuss the systematic discrepancy between O-type stellar masses derived from spectroscopic models and those derived from evolutionary tracks. Most likely, the cause of this 'mass discrepancy' lies primarily in the atmospheric models, which are plane parallel and hydrostatic and therefore do not account for an extended atmosphere and the velocity fields in a stellar wind. Finally, we present a new computation of the Lyman-continuum luminosity from 429 known O stars located within 2.5 kpc of the Sun. We find the total ionizing luminosity from this population ((Q(sub 0)(sup T(sub ot))) = 7.0 x 10(exp 51) photons/s) to be 47% larger than that determined using the Lyman continuum values tabulated by Panagia.

  2. CIRCUMBINARY PLANETS ORBITING THE RAPIDLY PULSATING SUBDWARF B-TYPE BINARY NY Vir

    SciTech Connect

    Qian, S.-B.; Zhu, L.-Y.; Dai, Z.-B.; He, J.-J.; Xiang, F.-Y.

    2012-02-15

    We report here the tentative discovery of a Jovian planet in orbit around the rapidly pulsating subdwarf B-type (sdB-type) eclipsing binary NY Vir. By using newly determined eclipse times together with those collected from the literature, we detect that the observed-calculated (O - C) curve of NY Vir shows a small-amplitude cyclic variation with a period of 7.9 yr and a semiamplitude of 6.1 s, while it undergoes a downward parabolic change (revealing a period decrease at a rate of P-dot = -9.2 x 10{sup -12}). The periodic variation was analyzed for the light-travel-time effect via the presence of a third body. The mass of the tertiary companion was determined to be M{sub 3}sin i' = 2.3({+-} 0.3)M{sub Jupiter} when a total mass of 0.60 M{sub Sun} for NY Vir is adopted. This suggests that it is most probably a giant circumbinary planet orbiting NY Vir at a distance of about 3.3 astronomical units (AU). Since the rate of period decrease cannot be explained by true angular momentum loss caused by gravitational radiation or/and magnetic braking, the observed downward parabolic change in the O - C diagram may be only a part of a long-period (longer than 15 years) cyclic variation, which may reveal the presence of another Jovian planet ({approx}2.5 M{sub Jupiter}) in the system.

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

    PubMed

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

    2013-01-01

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

  4. Effect of chronic treatment with deoxycorticosterone acetate on content of a natriuretic substance in atria of rats.

    PubMed

    Hathaway, S J; Fregly, M J; Wilson, K M; Papanek, P E; Henley, W N

    1986-10-01

    Chronic (72 days) administration of deoxycorticosterone acetate (DOCA), with or without saline as the sole drinking fluid, depleted atria of rats of their diuretic and natriuretic activities. Chronic ingestion of saline as the sole drinking fluid did not affect the diuretic, natriuretic, and kaliuretic activities of atria compared with those of rats receiving water to drink. Since systolic blood pressure of the DOCA-treated group did not differ significantly from that of the untreated control group, the decrease in potency of atrial extract from DOCA-treated rats most likely occurred in response to increases in extracellular and vascular volumes. The ability of DOCA to decrease diuretic and natriuretic activities of atria was dose dependent. The decreased activities of the atria of DOCA-treated rats could reflect an increased production and turnover of atrial natriuretic factor. Additional studies revealed an increased diuretic and natriuretic responsiveness of DOCA-treated recipients to atrial extract from untreated rats. Thus, the results of these studies suggest that chronic treatment with DOCA reduced the natriuretic and diuretic potencies of atrial extract and increased renal responsiveness to it.

  5. The Accuracy of Natriuretic Peptides (BNP and NT-pro-BNP) in the Differentiation between Transfusion Related Acute Lung Injury (TRALI) and Transfusion Related Circulatory Overload (TACO) in the Critically Ill

    PubMed Central

    Li, Guangxi; Daniels, Craig E.; Kojicic, Marija; Krpata, Tami; Wilson, Greg A; Winters, Jeffrey L; Moore, S Breanndan; Gajic, Ognjen

    2009-01-01

    BACKGROUND The diagnostic workup of TRALI requires an exclusion of TACO. Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic (NT-pro-BNP) accurately diagnosed TACO in preliminary studies that did not include patients with TRALI. STUDY DESIGN AND METHODS In this prospective cohort study two critical care experts blinded to serum levels of BNP and NT-pro-BNP determined the diagnosis of TRALI, TACO, and possible TRALI based on the consensus conference definitions. The accuracy of BNP and NT-pro-BNP was assessed based on the area under the receiver operating curve (AUC). RESULTS Of 115 patients who developed acute pulmonary edema after transfusion, 34 were identified with TRALI, 31 with possible TRALI, and 50 with TACO. Median BNP was 375pg/mL (interquartile range [IQR], 122.5 to 780.5pg/mL) in TRALI, 446pg/mL (IQR, 128 to 743.3pg/mL) in possible TRALI and 559pg/mL (IQR, 287.8 to 1347.8pg/mL) in TACO patients (p=0.038). The NT-pro-BNP levels among patients with TRALI, possible TRALI and TACO differed significantly with a median value of 1558.5pg/mL(IQR, 628.5 to 5114pg/mL), 2349pg/mL(IQR, 919 to 4610pg/mL) and 5197pg/mL(IQR, 1695 to 15714pg/mL)(p=0.0036), respectively. The accuracy of BNP and NT-pro-BNP to diagnose TACO was moderate with an area under curve (AUC) of 0.63(95% confidence interval [CI] 0.51 to 0.74) and 0.70(95%CI 0.59 to 0.80). CONCLUSIONS Natriuretic peptides are of limited diagnostic value in a differential diagnosis of pulmonary edema after transfusion in the critically ill patients. PMID:18954397

  6. The nature of the late B-type stars HD 67044 and HD 42035

    NASA Astrophysics Data System (ADS)

    Monier, R.; Gebran, M.; Royer, F.

    2016-04-01

    While monitoring a sample of apparently slowly rotating superficially normal bright late B and early A stars in the northern hemisphere, we have discovered that HD 67044 and HD 42035, hitherto classified as normal late B-type stars, are actually respectively a new chemically peculiar star and a new spectroscopic binary containing a very slow rotator HD 42035 S with ultra-sharp lines (v_{{e}}sin i= 3.7 km s^{-1}) and a fast rotator HD 42035 B with broad lines. The lines of Ti ii, Cr ii, Mn ii, Sr ii, Y ii, Zr ii and Ba ii are conspicuous features in the high resolution SOPHIE spectrum (R=75000) of HD 67044. The Hg ii line at 3983.93 Å is also present as a weak feature. The composite spectrum of HD 42035 is characterised by very sharp lines formed in HD 42035 S superimposed onto the shallow and broad lines of HD 42035 B. These very sharp lines are mostly due to light elements from C to Ni, the only heavy species definitely present are strontium and barium. Selected lines of 21 chemical elements from He up to Hg have been synthesized using model atmospheres computed with ATLAS9 and the spectrum synthesis code SYNSPEC48 including hyperfine structure of various isotopes when relevant. These synthetic spectra have been adjusted to high resolution high signal-to-noise spectra of HD 67044 and HD 42035 S in order to derive abundances of these key elements. HD 67044 is found to have distinct enhancements of Ti, Cr, Mn, Sr, Y, Zr, Ba and Hg and underabundances in He, C, O, Ca and Sc which shows that this star is not a superficially normal late B-type star, but actually is a new CP star most likely of the HgMn type. HD 42035 S has provisional underabundances of the light elements from C to Ti and overabundances of heavier elements (except for Fe and Sr which are also underabundant) up to barium. These values are lower limits to the actual abundances as we cannot currently place properly the continuum of HD 42035 S. More accurate fundamental parameters and abundances for HD

  7. Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

    PubMed Central

    Seidah, N G; Lazure, C; Chrétien, M; Thibault, G; Garcia, R; Cantin, M; Genest, J; Nutt, R F; Brady, S F; Lyle, T A

    1984-01-01

    A substance called atrial natriuretic factor (ANF), localized in secretory granules of atrial cardiocytes, was isolated as four homologous natriuretic peptides from homogenates of rat atria. The complete sequence of the longest form showed that it is composed of 33 amino acids. The three other shorter forms (2-33, 3-33, and 8-33) represent amino-terminally truncated versions of the 33 amino acid parent molecule as shown by analysis of sequence, amino acid composition, or both. The proposed primary structure agrees entirely with the amino acid composition and reveals no significant sequence homology with any known protein or segment of protein. The short form ANF-(8-33) was synthesized by a multi-fragment condensation approach and the synthetic product was shown to exhibit specific activity comparable to that of the natural ANF-(3-33). PMID:6232612

  8. Maintaining the Phenotype Stability of Chondrocytes Derived from MSCs by C-Type Natriuretic Peptide

    PubMed Central

    Shi, Quan; Qian, Zhiyong; Liu, Donghua; Sun, Jie; Xu, Juan; Guo, Ximin

    2017-01-01

    Mesenchymal stem cells (MSCs) play a critical role in cartilage tissue engineering. However, MSCs-derived chondrocytes or cartilage tissues are not stable and easily lose the cellular and cartilage phenotype during long-term culture in vitro or implantation in vivo. As a result, chondrocytes phenotypic instability can contribute to accelerated ossification. Thus, it is a big challenge to maintain their correct phenotype for engineering hyaline cartilage. As one member of the natriuretic peptide family, C-type natriuretic peptide (CNP) is found to correlate with the development of the cartilage, affect the chondrocytes proliferation and differentiation. Besides, based on its biological effects on protection of extracellular matrix of cartilage and inhibition of mineralization, we hypothesize that CNP may contribute to the stability of chondrocyte phenotype of MSCs-derived chondrocytes. PMID:28337152

  9. Natriuretic peptide type C induces sperm attraction for fertilization in mouse

    PubMed Central

    Kong, Nana; Xu, Xiaoting; Zhang, Yu; Wang, Yakun; Hao, Xiaoqiong; Zhao, Yu; Qiao, Jie; Xia, Guoliang; Zhang, Meijia

    2017-01-01

    Mammalian spermatozoa undergo selective movement along the isthmus of the oviduct to the ampulla during ovulation, which is a prerequisite for fertilization. The factor(s) that involves in selective spermatozoa movement is still unknown. In this study, we found that the oviductal epithelium in mouse ampulla expressed high levels of natriuretic peptide type C (NPPC) in the presence of ovulated oocyte-cumulus complexes (OCCs). Spermatozoa expressed NPPC receptor natriuretic peptide receptor 2 (NPR2, a guanylyl cyclase) on the midpiece of flagellum. NPPC increased intracellular levels of cGMP and Ca2+ of spermatozoa, and induced sperm accumulation in the capillary by attraction. Importantly, spermatozoa from Npr2 mutant mice were not attracted by NPPC, preventing fertilization in vivo. Oocyte-derived paracrine factors promoted the expression of Nppc mRNA in the ampulla. Therefore, NPPC secreted by oviductal ampulla attracts spermatozoa towards oocytes, which is essential for fertilization. PMID:28054671

  10. Atrial natriuretic factor inhibits mitogen-induced growth in aortic smooth muscle cells.

    PubMed

    Baldini, P M; De Vito, P; Fraziano, M; Mattioli, P; Luly, P; Di Nardo, P

    2002-10-01

    Atrial natriuretic factor (ANF) is a polypeptide able to affect cardiovascular homeostasis exhibiting diuretic, natriuretic, and vasorelaxant activities. ANF shows antimitogenic effects in different cell types acting through R(2) receptor. Excessive proliferation of smooth muscle cells is a common phenomenon in diseases such as atherosclerosis, but the role of growth factors in the mechanism which modulate this process has yet to be clarified. The potential antimitogenic role of ANF on the cell growth induced by growth factors appears very intriguing. Aim of the present study was to investigate the possible involvement of ANF on rat aortic smooth muscle (RASM) cells proliferation induced by known mitogens and the mechanism involved. Our data show that ANF, at physiological concentration range, inhibits RASM cell proliferation induced by known mitogens such as PDGF and insulin, and the effect seems to be elicited through the modulation of phosphatidic acid (PA) production and MAP kinases involvement.

  11. [Assessment of natriuretic peptide indices and oxidative stress in patients with chronic heart failure].

    PubMed

    Abezov, D K; Kamilova, U K; Shukurdzhanova, S M; Rakhmonov, R R; Alieva, T A

    2010-01-01

    The authors have studied indices of natriuretic peptide and oxidative stress in patients with chronic heart failure (CHF). 52 male patients with postinfarction cardiosclerosis (PICS) who have developed CHF have been observed. The age of the patients varied from 38 till 60. It was established that CHF patients with progression of the disease had worsening of their clinical condition together with an increase of oxidative stress which was characterized through decrease of NO metabolites, NADPH--diaphorase (eNOS), increase of nitrite reductase (iNOS) and peroxinitrite (ONOO), correlative increase the level of brain natriuretic peptide in blood plazma. Reliable connection between considerable increase of oxidative stress and the level of NT-pro BNP was noted in CHF patients, which demands necessity of correction of observed disorders.

  12. Cytochrome P4504A inhibitors attenuate the exaggerated natriuretic response to volume expansion in thyroidectomized rats

    PubMed Central

    Colombero, Cecilia; Venara, Marcela; Gonzalez, Daniel; Roman, Richard J.; Nowicki, Susana

    2014-01-01

    Abstract Thyroidectomy augments the natriuretic response to volume expansion; however, the mechanism remains unknown. This study assessed the role of 20‐hydroxyeicosatetraenoic acid (20‐HETE) in the natriuretic response to an acute volume expansion in hypothyroid rats. Urine flow (1.9‐fold), sodium excretion (2.4‐fold), fractional sodium excretion (3.8‐fold), and distal delivery of sodium (4.1‐fold) increased to a greater extent in thyroidectomized rats (TX) than in sham‐operated controls (SHAM) following i.v. infusion of isotonic saline (5% body weight) over 60 min. This was associated with inhibition of both proximal and distal tubular reabsorption of sodium. Administration of two mechanistic and chemical dissimilar inhibitors of the synthesis of 20‐HETE, 1‐aminobenzotriazole (ABT), and N‐hydroxy‐N’‐(‐4‐butyl‐2‐methylphenyl)formamidine (HET0016) decreased the natriuretic response in TX rats. Glomerular filtration rate was lower in TX than in SHAM rats and was not altered by the CYP4A inhibitors. The expression, intrarenal distribution, and the formation of 20‐HETE and expoxygenase metabolites of arachidonic acid were similar in the cortex and medulla of SHAM and TX rats. These results suggest that CYP4A‐derived metabolites of arachidonic acid play an important role in the enhanced natriuretic response to volume expansion in hypothyroid rats even though TX did not alter the expression or activity of these enzymes. PMID:24920124

  13. Natriuretic hormone—its possible role in fluid and electrolyte disturbances in chronic liver disease

    PubMed Central

    Kramer, Herbert J.

    1975-01-01

    Besides intrarenal physical factors and aldosterone, a natriuretic hormone has been postulated to modulate renal tubular sodium resorption in order to maintain body fluid homeostasis. To investigate the possible role of a natriuretic activity in sodium retention of chronic liver disease, the effects of plasma and plasma fraction IV from patients with cirrhosis of the liver and ascites on sodium transport of the isolated frog skin and on renal sodium excretion in the rat were compared to the antinatriferic and natriuretic effects of plasma from healthy subjects. While plasma from healthy individuals obtained following acute expansion of the extracellular fluid volume (ECV) significantly inhibited potential difference (PD) by -43·8 ± 5·5% and short circuit current (SCC) by -41·3 ± 1·7% when applied to the inner skin surface, control plasma and plasma from patients with liver cirrhosis and ascites affected PD by -3·8 ± 4·7% and -5·2 ± 3·7% and SCC by -7·3 ± 4·6% and -11·7 ± 2·5% respectively. Similar effects on PD and SCC were observed with plasma fractions IV. In contrast to fraction IV from ECV-expanded individuals, which caused marked diuresis and natriuresis when injected in the rat, fraction IV of plasma from cirrhotic patients failed to affect urinary flow rate, free-water clearance or renal sodium excretion. The results suggest that at least some patients with cirrhosis of the liver and sodium retention may lack an adequate humoral natriuretic activity sufficiently to promote renal sodium excretion. PMID:1234337

  14. Specific receptor binding of atrial natriuretic peptide to rat renal cortex

    SciTech Connect

    Ogura, T.; Mitsui, T.; Ogawa, N.; Ota, Z.

    1985-09-01

    Radiolabeled receptor assay (RRA) of atrial natriuretic peptide (ANP) was studied in rat kidney membranes. Binding of ( SVI)-ANP to membrane preparations of rat whole kidney was saturated and show a high affinity. Furthermore, renal cortex membrane had a higher affinity for ANP binding site than renal medulla membrane. This high affinity ANP receptor site in renal cortex membrane indicated that ANP controlled the balance of water and sodium excretion due to this receptor site in the kidney.

  15. Discovery and dimeric approach of novel Natriuretic Peptide Receptor A (NPR-A) agonists.

    PubMed

    Iwaki, Takehiko; Oyama, Yoshiaki; Tomoo, Toshiyuki; Tanaka, Taisaku; Okamura, Yoshihiko; Sugiyama, Masako; Yamaki, Akira; Furuya, Mayumi

    2017-03-15

    Novel agonists of the Natriuretic Peptide Receptor A (NPR-A) were obtained through random screening and subsequent structural modification of triazine derivatives. The key structural feature to improve in vitro activity was the dimerization of triazine monomer derivatives. The non peptide derivative 7c and 13a showed highly potent NPR-A agonistic activity in vitro and diuretic activity in vivo. These results implied that non-peptidic small molecules open the possibility of new therapy for congestive heart failure.

  16. Natriuretic Peptide Receptor A as a Novel Target for Prostate Cancer

    PubMed Central

    2011-01-01

    Background The receptor for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPRA), is expressed in cancer cells, and natriuretic peptides have been implicated in cancers. However, the direct role of NPRA signaling in prostate cancer remains unclear. Results NPRA expression was examined by western blotting, RT-PCR and immunohistochemistry. NPRA was downregulated by transfection of siRNA, shRNA and NPRA inhibitor (iNPRA). Antitumor efficacy of iNPRA was tested in mice using a TRAMP-C1 xenograft. Here, we demonstrated that NPRA is abundantly expressed on tumorigenic mouse and human prostate cells, but not in nontumorigenic prostate epithelial cells. NPRA expression showed positive correlation with clinical staging in a human PCa tissue microarray. Down-regulation of NPRA by siNPRA or iNPRA induced apoptosis in PCa cells. The mechanism of iNPRA-induced anti-PCa effects was linked to NPRA-induced expression of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine over-expressed in PCa and significantly reduced by siNPRA. Prostate tumor cells implanted in mice deficient in atrial natriuretic peptide receptor A (NPRA-KO) failed to grow, and treatment of TRAMP-C1 xenografts with iNPRA reduced tumor burden and MIF expression. Using the TRAMP spontaneous PCa model, we found that NPRA expression correlated with MIF expression during PCa progression. Conclusions Collectively, these results suggest that NPRA promotes PCa development in part by regulating MIF. Our findings also suggest that NPRA is a potential prognostic marker and a target for PCa therapy. PMID:21586128

  17. Interferon alpha bioactivity critically depends on Scavenger receptor class B type I function

    PubMed Central

    Vasquez, Marcos; Fioravanti, Jessica; Aranda, Fernando; Paredes, Vladimir; Gomar, Celia; Ardaiz, Nuria; Fernandez-Ruiz, Veronica; Méndez, Miriam; Nistal-Villan, Estanislao; Larrea, Esther; Gao, Qinshan; Gonzalez-Aseguinolaza, Gloria; Prieto, Jesus; Berraondo, Pedro

    2016-01-01

    ABSTRACT Scavenger receptor class B type I (SR-B1) binds pathogen-associated molecular patterns participating in the regulation of the inflammatory reaction but there is no information regarding potential interactions between SR-B1 and the interferon system. Herein, we report that SR-B1 ligands strongly regulate the transcriptional response to interferon α (IFNα) and enhance its antiviral and antitumor activity. This effect was mediated by the activation of TLR2 and TLR4 as it was annulled by the addition of anti-TLR2 or anti-TLR4 blocking antibodies. In vivo, we maximized the antitumor activity of IFNα co-expressing in the liver a SR-B1 ligand and IFNα by adeno-associated viruses. This gene therapy strategy eradicated liver metastases from colon cancer with reduced toxicity. On the other hand, genetic and pharmacological inhibition of SR-B1 blocks the clathrin-dependent interferon receptor recycling pathway with a concomitant reduction in IFNα signaling and bioactivity. This effect can be applied to enhance cancer immunotherapy with oncolytic viruses. Indeed, SR-B1 antagonists facilitate replication of oncolytic viruses amplifying their tumoricidal potential. In conclusion, SR-B1 agonists behave as IFNα enhancers while SR-B1 inhibitors dampen IFNα activity. These results demonstrate that SR-B1 is a suitable pharmacology target to enhance cancer immunotherapy based on IFNα and oncolytic viruses. PMID:27622065

  18. Facile synthesis of B-type carbonated nanoapatite with tailored microstructure

    NASA Astrophysics Data System (ADS)

    Gualtieri, Magdalena Lassinantti; Romagnoli, Marcello; Hanuskova, Miriam; Fabbri, Elena; Gualtieri, Alessandro F.

    2014-12-01

    Nanolime and a phosphate-based chelating agent were used to synthesize B-type carbonated apatite. Developed Rietveld refinement strategies allowed one to determine process yield, product crystallinity as well as structural (unit cell) and microstructural (size, strain) parameters. The effect of synthesis temperature (20-60 °C) as well as Ca/P ratio (1.5-2.5) and solid content (10-30 wt%) of the starting batch on these properties were investigated. FTIR, TEM and gas adsorption data provided supporting evidence. The process yield was 42-60 wt% and found to be governed by the Ca/P ratio. The purified products had high specific surface area (107-186 m2/g) and crystallinity (76-97%). The unit cell parameters, correlated to the degree of structural carbonate, were sensitive to the Ca/P ratio. Instead, temperature governed the microstructural parameters. Less strained and larger crystals were obtained at higher temperatures. Long-term aging up to 6 months at 20 °C compensated for higher crystal growth kinetics at higher temperature.

  19. Emergent criticality in complex turing B-type atomic switch networks.

    PubMed

    Stieg, Adam Z; Avizienis, Audrius V; Sillin, Henry O; Martin-Olmos, Cristina; Aono, Masakazu; Gimzewski, James K

    2012-01-10

    Recent advances in the neuromorphic operation of atomic switches as individual synapse-like devices demonstrate the ability to process information with both short-term and long-term memorization in a single two terminal junction. Here it is shown that atomic switches can be self-assembled within a highly interconnected network of silver nanowires similar in structure to Turing’s “B-Type unorganized machine”, originally proposed as a randomly connected network of NAND logic gates. In these experimental embodiments,complex networks of coupled atomic switches exhibit emergent criticality similar in nature to previously reported electrical activity of biological brains and neuron assemblies. Rapid fluctuations in electrical conductance display metastability and power law scaling of temporal correlation lengths that are attributed to dynamic reorganization of the interconnected electro-ionic network resulting from induced non-equilibrium thermodynamic instabilities. These collective properties indicate a potential utility for realtime,multi-input processing of distributed sensory data through reservoir computation. We propose these highly coupled, nonlinear electronic networks as an implementable hardware-based platform toward the creation of physically intelligent machines.

  20. PULSATING B-TYPE STARS IN THE OPEN CLUSTER NGC 884: FREQUENCIES, MODE IDENTIFICATION, AND ASTEROSEISMOLOGY

    SciTech Connect

    Saesen, S.; Briquet, M.; Aerts, C.; Carrier, F.; Miglio, A.

    2013-10-01

    Recent progress in the seismic interpretation of field β Cep stars has resulted in improvements of the physical description in the stellar structure and evolution model computations of massive stars. Further asteroseismic constraints can be obtained from studying ensembles of stars in a young open cluster, which all have similar age, distance, and chemical composition. We present an observational asteroseismology study based on the discovery of numerous multi-periodic and mono-periodic B stars in the open cluster NGC 884. We describe a thorough investigation of the pulsational properties of all B-type stars in the cluster. Overall, our detailed frequency analysis resulted in 115 detected frequencies in 65 stars. We found 36 mono-periodic, 16 bi-periodic, 10 tri-periodic, and 2 quadru-periodic stars and one star with nine independent frequencies. We also derived the amplitudes and phases of all detected frequencies in the U, B, V, and I filter, if available. We achieved unambiguous identifications of the mode degree for 12 of the detected frequencies in nine of the pulsators. Imposing the identified degrees and measured frequencies of the radial, dipole, and quadrupole modes of five pulsators led to a seismic cluster age estimate of log (age/yr) = 7.12-7.28 from a comparison with stellar models. Our study is a proof-of-concept for and illustrates the current status of ensemble asteroseismology of a young open cluster.

  1. WW Geminorum: An early B-type eclipsing binary evolving into the contact phase

    SciTech Connect

    Yang, Y.-G.; Dai, H.-F.; Yin, X.-G.; Yang, Y. E-mail: yangyg@chnu.edu.cn

    2014-11-01

    WW Gem is a B-type eclipsing binary with a period of 1.2378 days. The CCD photometry of this binary was performed in 2013 December using the 85 cm telescope at the Xinglong Stations of the National Astronomical Observatories of China. Using the updated W-D program, the photometric model was deduced from the VRI light curves. The results imply that WW Gem is a near-contact eclipsing binary whose primary component almost fills its Roche lobe. The photometric mass ratio is q {sub ph} = 0.48(± 0.05). All collected times of minimum light, including two new ones, were used for the period studies. The orbital period changes of WW Gem could be described by an upward parabola, possibly overlaid by a light-time orbit with a period of P {sub mod} = 7.41(± 0.04) yr and a semi-amplitude of A = 0.0079 days(± 0.0005 days), respectively. This kind of cyclic oscillation may be attributed to the light-travel time effect via the third body. The long-term period increases at a rate of dP/dt = +3.47(±0.04) × 10{sup –8} day yr{sup –1}, which may be explained by the conserved mass transfer from the less massive component to the more massive one. With mass transfer, the massive binary WW Gem may be evolving into a contact binary.

  2. Regulation of expression of atrial and brain natriuretic peptide, biomarkers for heart development and disease.

    PubMed

    Sergeeva, Irina A; Christoffels, Vincent M

    2013-12-01

    The mammalian heart expresses two closely related natriuretic peptide (NP) hormones, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The excretion of the NPs and the expression of their genes strongly respond to a variety of cardiovascular disorders. NPs act to increase natriuresis and decrease vascular resistance, thereby decreasing blood volume, systemic blood pressure and afterload. Plasma levels of BNP are used as diagnostic and prognostic markers for hypertrophy and heart failure (HF), and both ANF and BNP are widely used in biomedical research to assess the hypertrophic response in cell culture or the development of HF related diseases in animal models. Moreover, ANF and BNP are used as specific markers for the differentiating working myocardium in the developing heart, and the ANF promoter serves as platform to investigate gene regulatory networks during heart development and disease. However, despite decades of research, the mechanisms regulating the NP genes during development and disease are not well understood. Here we review current knowledge on the regulation of expression of the genes for ANF and BNP and their role as biomarkers, and give future directions to identify the in vivo regulatory mechanisms. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.

  3. Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.

    PubMed

    Gelfand, R A; Frank, H J; Levin, E; Pedram, A

    1991-08-01

    The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.

  4. Reduced ability of C-type natriuretic peptide (CNP) to activate natriuretic peptide receptor B (NPR-B) causes dwarfism in lbab -/- mice.

    PubMed

    Yoder, Andrea R; Kruse, Andrew C; Earhart, Cathleen A; Ohlendorf, Douglas H; Potter, Lincoln R

    2008-09-01

    C-type natriuretic peptide (CNP) stimulates endochondrial ossification by activating the transmembrane guanylyl cyclase, natriuretic peptide receptor-B (NPR-B). Recently, a spontaneous autosomal recessive mutation that causes severe dwarfism in mice was identified. The mutant, called long bone abnormality (lbab), contains a single point mutation that converts an arginine to a glycine in a conserved coding region of the CNP gene, but how this mutation affects CNP activity has not been reported. Here, we determined that 30-fold to greater than 100-fold more CNP(lbab) was required to activate NPR-B as compared to wild-type CNP in whole cell cGMP elevation and membrane guanylyl cyclase assays. The reduced ability of CNP(lbab) to activate NPR-B was explained, at least in part, by decreased binding since 10-fold more CNP(lbab) than wild-type CNP was required to compete with [125I][Tyr0]CNP for receptor binding. Molecular modeling suggested that the conserved arginine is critical for binding to an equally conserved acidic pocket in NPR-B. These results indicate that reduced binding to and activation of NPR-B causes dwarfism in lbab(-/-) mice.

  5. Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting

    PubMed Central

    Youmans, Steven J; Fein, Miriam R; Wirkowski, Elizabeth; Maesaka, John K

    2013-01-01

    We have utilized the persistent elevation of fractional excretion (FE) of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW) from the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which a normalization of FEurate occurs after correction of hyponatremia.  Previous studies suggest as well  that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients.  The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity.   Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff) to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients) or with SIADH (2 patients). Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW.  Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future experimental

  6. Thermomagnetic treatment effects on microstructure in Nd-Fe-B type sintered magnets

    NASA Astrophysics Data System (ADS)

    PaigeSmith, Catherine

    Optimizing the microstructure of sintered Nd-Fe-B type magnets has become increasingly important. Sintered magnets are key components to the growing industry of alternative energy, particularly wind turbines and electric car generators. With rising costs and limited supply of rare earth elements, special attention has been dedicated to improving magnetic properties of these magnets through processing rather than compositional modifications. The magnetic property needing the most improvement in Nd-Fe-B type sintered magnets is coercivity. Coercivity dictates the performance of magnets at temperatures still below the demagnetizing threshold temperature. It has been shown that annealing sintered magnets in a magnetic field can enhance coercivity when compared to conventional post-sinter annealing in the absence of a magnetic field. However, little is known about the microstructural changes that occur in sintered magnets as a result of these thermo-magnetic treatments. This work presents themicrostructural characterization of Dy-free and Dy-containing sintered magnets that have undergone annealing in a magnetic field of 9T. Microstructural characterization techniques were used to identify phases, analyze the texture of phases identified, and to study intergranular phases. Microstructural findings were then used to propose a solidification scheme during annealing and connect such findings to magnetic property results, as well as to make suggestions for optimizing the manufacturing process. In addition to the magnetic phase, phases identified in the Dy-free and Dy-containing Nd-Fe-B sintered magnets consisted of Nb-rich precipitates, Nd-rich phases, and phases from the Nd-Fe-Cu ternary system. Nd-Fe-Cu phases included alpha-Nd, NdCu, and the tau (Nd6Fe13Cu). The Nd-rich phases were specifically identified to be NdOx precipitates in an alpha-Nd matrix, and contained an orientation relationship described by (0001)alpha-Nd||(111)NdOx and [112¯0]alpha-Nd||[1¯10]NdO x. This

  7. Scavenger receptor class B, type I (Scarb1) deficiency promotes osteoblastogenesis but stunts terminal osteocyte differentiation

    PubMed Central

    Martineau, Corine; Kevorkova, Olha; Brissette, Louise; Moreau, Robert

    2014-01-01

    Abstract Scavenger receptor class B type I (SR‐BI), the Scarb1 gene product, is a high‐density lipoprotein (HDL) receptor which was shown to influence bone metabolism. Its absence in mice is associated with alterations of the glucocorticoid/adrenocorticotropic hormone axis, and translated in high bone mass and enhanced bone formation. Since the cellular alterations underlying the enhanced bone formation remain unknown, we investigated Scarb1‐deficient marrow stromal cells (MSC) behavior in vitro. No difference in HDL3, cholesteryl ester (CE) or estradiol (E) association/binding was measured between Scarb1‐null and wild‐type (WT) cells. Scarb1 genic expression was down‐regulated twofold following osteogenic treatment. Neither WT nor null cell proliferation was influenced by HDL3 exposure whereas this condition decreased genic expression of osteoblastic marker osterix (Sp7), and osteocyte markers sclerostin (Sost) and dentin matrix protein 1 (Dmp1) independently of genotype. Sost and Dmp1 basal expression in null cells was 40% and 50% that of WT cells; accordingly, osteocyte density was 20% lower in vertebrae from Scarb1‐null mice. Genic expression of co‐receptors for Wnt signaling, namely LDL‐related protein (Lrp) 5 and Lrp8, was increased, respectively, by two‐ and threefold, and of transcription target‐genes axis inhibition protein 2 (Axin2) and lymphoid enhancer‐binding factor 1 (Lef1) over threefold. Gene expression of Wnt signaling agonist Wnt5a and of the antagonist dickkopfs‐related protein 1 (Dkk1) were found to be increased 10‐ to 20‐fold in null MSC. These data suggest alterations of Wnt pathways in Scarb1‐deficient MSC potentially explaining their enhanced function, hence contributing to the high bone mass observed in these mice. PMID:25281615

  8. Facile synthesis of B-type carbonated nanoapatite with tailored microstructure

    SciTech Connect

    Gualtieri, Magdalena Lassinantti; Romagnoli, Marcello; Hanuskova, Miriam; Fabbri, Elena; Gualtieri, Alessandro F.

    2014-12-15

    Nanolime and a phosphate-based chelating agent were used to synthesize B-type carbonated apatite. Developed Rietveld refinement strategies allowed one to determine process yield, product crystallinity as well as structural (unit cell) and microstructural (size, strain) parameters. The effect of synthesis temperature (20–60 °C) as well as Ca/P ratio (1.5–2.5) and solid content (10–30 wt%) of the starting batch on these properties were investigated. FTIR, TEM and gas adsorption data provided supporting evidence. The process yield was 42–60 wt% and found to be governed by the Ca/P ratio. The purified products had high specific surface area (107–186 m{sup 2}/g) and crystallinity (76–97%). The unit cell parameters, correlated to the degree of structural carbonate, were sensitive to the Ca/P ratio. Instead, temperature governed the microstructural parameters. Less strained and larger crystals were obtained at higher temperatures. Long-term aging up to 6 months at 20 °C compensated for higher crystal growth kinetics at higher temperature. - Graphical abstract: Controlled synthesis of carbonated apatite at moderate temperatures using nanolime and sodiumhexametaphosphate as starting reagent. - Highlights: • Chemical synthesis of nano-sized apatite with tailored microstructure was performed. • Colloidal Ca(OH){sub 2} and a phosphorus-based chelating agents were used as reagents. • The method is simple and reproducible which facilitate industrial process scale-up. • Rietveld refinement strategies for product characterization were developed. • Rietveld analyses provided yield, microstructural and structure information.

  9. Plasma proatrial natriuretic factor (1-98) concentration after myocardial infarction: relation to indices of cardiac and renal function.

    PubMed Central

    Bonarjee, V. V.; Omland, T.; Nilsen, D. W.; Caidahl, K.; Sundsfjord, J. A.; Dickstein, K.

    1995-01-01

    OBJECTIVES--(a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN--Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING--Norwegian central hospital. PATIENTS--Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES--Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS--Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection

  10. Expression of the atrial natriuretic peptide gene in the cardiac muscle of rat extrapulmonary and intrapulmonary veins.

    PubMed Central

    Springall, D R; Bhatnagar, M; Wharton, J; Hamid, Q; Gulbenkian, S; Hedges, M; Meleagros, L; Bloom, S R; Polak, J M

    1988-01-01

    Atrial natriuretic peptide is a peptide regulating salt and water balance, originally isolated from the cardiac atrium, where it is synthesised as part of a precursor molecule in specialised myocardial cells. The myocardium extends into the extrapulmonary part of the pulmonary veins in many species, including man. In some small mammals, however, such as the rat, mouse, and bat, it extends further to veins in the peripheral parts of the lung. Since this myocardial layer is continuous with that in the atrium, we have looked for the possible expression of the atrial natriuretic peptide gene in this tissue in rats. Strong immunoreactivity was seen for both the peptide and the N terminal sequence (cardiodilatin) of its precursor in extrapulmonary veins and in intrapulmonary veins extending into the lung as far as the second branching point, where it was localised in the dense cored granules by electron microscopy; in situ hybridisation showed atrial natriuretic peptide messenger RNA at identical sites. Chromatography and radioimmunoassay of extracts of extrapulmonary and intrapulmonary veins showed most of the atrial natriuretic peptide immunoreactivity to be in the uncleaved (precursor molecule) form. Thus the peptide is synthesised in veins both outside and inside the lung, and these extra-atrial sites may be an important additional source of circulating atrial natriuretic peptide. Images PMID:2965426

  11. Increase in plasma concentrations of cardiodilatin (amino terminal pro-atrial natriuretic peptide) in cardiac failure and during recumbency.

    PubMed Central

    Meleagros, L; Gibbs, J S; Ghatei, M A; Bloom, S R

    1988-01-01

    Plasma concentrations of cardiodilatin, the peptide sequence at the amino terminal of the pro-atrial natriuretic peptide, in 17 normal subjects ranged from 59 to 202 (mean 118 (SEM) (9] pmol/l. Recumbency increased the mean (SEM) concentration to 160 (13) pmol/l. The plasma concentration of cardiodilatin in 24 patients with congestive cardiac failure was much higher (964 (175) pmol/l) than in the normal subjects. It was highest in those with heart failure in New York Heart Association functional classes III and IV and the concentration correlated both with atrial natriuretic peptide concentrations and left ventricular ejection fraction. Concentrations rose during induced tachycardia in three patients tested. Chromatography showed a single clean peak of plasma cardiodilatin immunoreactivity. It seems that cardiodilatin is a second circulating cardiac peptide that is jointly released with atrial natriuretic peptide by common stimuli. Other workers have reported that, like atrial natriuretic peptide, three partial cardiodilatin sequences can stimulate renal particulate guanylate cyclase and increase cyclic guanosine monophosphate. The simultaneous release of cardiodilatin in higher circulating concentrations than atrial natriuretic peptide may be relevant to the finding that appropriate concentrations of exogenous atrial natiuretic peptide alone do not produce the full renal effects associated with endogenous peptide release. PMID:2970269

  12. BNP and NT-proBNP Test

    MedlinePlus

    ... Peptides Formal name: B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide Related tests: Cardiac ... for B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) is ...

  13. Combination of drugs acting on the natriuretic system and the renin-angiotensin system in heart failure.

    PubMed

    Chee, Kok H; Amudha, Kadirvelu; Hussain, Nik A; Haizal, Haron K; Choy, Anna-Maria J; Lang, Chim C

    2003-09-01

    Conventional diuretic agents are very effective agents in relieving volume overload and congestive symptoms in chronic heart failure (CHF). However, they are associated with activation of the renin-angiotensin system (RAS) and the sympathetic nervous system and a reduction in glomerular filtration rate, all of which have been associated with adverse outcomes in CHF. Therefore, there is an increasing interest in drugs that target the natriuretic system without neurohormonal activation and deterioration of renal function. In this review, we will discuss the underlying rationale and evidence behind currently pursued strategies that target the natriuretic system. This includes the administration of natriuretic peptides (NPs) and strategies that potentiate the NP system, such as neutral endopeptidase inhibition. We will also highlight some potentially important interactions of these strategies with drugs that target the RAS.

  14. Effects of recombinant human brain natriuretic peptide on the prognosis of patients with acute anterior myocardial infarction undergoing primary percutaneous coronary intervention: a prospective, multi-center, randomized clinical trial

    PubMed Central

    Hou, Ai-Jie; Zang, Hong-Yun; Huang, Ru-Gang; Zheng, Xiao-Qun; Lin, Hai-Long; Wang, Wei; Hou, Ping; Xia, Fei; Li, Zhan-Quan

    2017-01-01

    Background This study aims to investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on serum enzyme data, cardiac function parameters and cardiovascular events in patients with acute anterior myocardial infarction (MI). Methods A total of 421 patients with acute anterior or extensive anterior MI were collected from 20 hospitals. These patients were randomly divided into two groups: rhBNP and control groups. Both groups of patients received primary percutaneous coronary intervention (PCI) within the effective time window. In the rhBNP group, rhBNP administration (0.01 µg/kg/min, 48–72 successive hours) was performed as early as possible after hospital admission. Prior to and one or seven days after PCI, serum concentrations of cardiac troponin (cTnT), creatine kinase-MB (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. At seven days and 6 months after PCI, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd) and stroke volume (SV) were measured using 2D Doppler echocardiography. MACEs that occurred during hospitalization and within 6 months after PCI were recorded. Results At postoperative days one and seven, serum concentrations of cTnT were significantly lower in the rhBNP group than in the control group. At postoperative day one, serum concentrations of CK-MB were significantly lower in the rhBNP group than in the control group. At postoperative day seven, serum concentrations of NT-proBNP were significantly lower in the rhBNP group than in the control group, and LVEF was significantly greater in the rhBNP group than in the control group. At postoperative 6 months, LVEDd was significantly lower in the rhBNP group compared with the control group. In addition, SV and LVEF were significantly greater in the rhBNP group than in the control group. By postoperative month 6, the incidence of composite cardiovascular events (16.0% vs. 26.0%, P=0.012), cardiac death (7.0% vs.13

  15. Natriuretic peptides in water-deprived and in salt-loaded rats.

    PubMed

    Makino, Y; Minamino, N; Kakishita, E; Kangawa, K; Matsuo, H

    1996-01-01

    To elucidate the differences of physiological function of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), we measured tissue concentration and mRNA level in cardiac atrium, ventricle, and brain as well as plasma concentration of these three peptides in water-deprived (WD) and in salt-loaded (SI.) rats. WD rats were given no water for 5 days, whereas SL rats had free access to 2% saline for 14 days. Plasma ANP and BNP concentration of the WD group decreased to 21% and < 10%, and the concentration of the SL group to 36% and 47% of the control (CON) group. Atrial and ventricular BNP concentration of the WD group decreased to 36% and 23% of the CON group, and atrial BNP concentration of the SL group decreased to a lesser extent. BNP mRNA level in atrium and ventricle decreased in both the WD and SL groups, with the WD group showing larger decreases to 11% and 20% of the CON group. ANP mRNA level in atrium and ventricle of the WD group decreased to 40% and 61% of the CON group, but increased to 147% in ventricle of the SL group. In the brain, no significant change was observed in ANP and CNP concentration in both the WD and SL group. Under these conditions. BNP generally showed larger changes than ANP in both peptide concentration and mRNA level. Gene transcription and peptide production of ANP and BNP in atrium and in ventricle were not always found to be in concert, especially in the case of salt loading. Taken as a whole, our results demonstrate differences among the systems regulating biosynthesis and secretion of ANP and BNP in atrium and ventricle.

  16. Atrial natriuretic factor mRNA and binding sites in the adrenal gland.

    PubMed Central

    Nunez, D J; Davenport, A P; Brown, M J

    1990-01-01

    The factor inhibiting aldosterone secretion produced by the adrenal medulla may be atrial natriuretic factor (ANF), since the latter abolishes aldosterone release in response to a number of secretagogues, including angiotensin II and K+. In this study we have shown that cells in the adrenal medulla contain ANF mRNA and therefore have the potential to synthesize this peptide. The presence of binding sites for ANF predominantly in the adrenal zona glomerulosa suggests that, if ANF is synthesized in the medulla and transferred to the cortex, it may affect mineralocorticoid status. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2146954

  17. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Huls, M. H.; Sams, Clarence F.

    1989-01-01

    In view of the suggestions by Chabrier et al. (1987) and Steardo and Nathanson (1987) that atrial natriuretic peptide (ANP) may play a role in the fluid homeostasis of the brain, the ANP receptors in primary cultures of bovine brain microvessel endothelian cells were quantitated and characterized. Results of partition binding studies and the effect of cGMP additions indicated the presence of at least two types of ANP receptors, with the majority of the receptors being the nonguanylate cyclase coupled receptors. The presence of at least two ANP receptor types suggests an active role for ANP in regulating brain endothelial cell function.

  18. Immunohistochemical localization of atrial natriuretic factor (ANF) in the excretory system of the rabbit parotid gland.

    PubMed

    Valentino, B; Farina Lipari, E; Carini, F; Valenza, V

    1999-01-01

    The immunohistochemical localization of atrial natriuretic factor (ANF) in the rabbit parotid gland was performed using an antibody against rabbit ANF and avidin-biotin or streptoavidin as detector. Results showed positivity in cuboidal and columnar cells of intralobular ducts and in basal cells of extralobular and main excretory duct. These data support the hypothesis that ANF produced by intralobular ducts could act through a paracrine mechanism; ANF produced by extralobular and main ducts may play a role in the regulation of salivary composition.

  19. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations

    PubMed Central

    Chen, Virginia; Hollander, Zsuzsanna; Leipsic, Jonathon A.; Hague, Cameron J.; DeMarco, Mari L.; FitzGerald, J. Mark; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.

    2017-01-01

    There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80). These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD. PMID:28328968

  20. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations.

    PubMed

    Chen, Yu-Wei Roy; Chen, Virginia; Hollander, Zsuzsanna; Leipsic, Jonathon A; Hague, Cameron J; DeMarco, Mari L; FitzGerald, J Mark; McManus, Bruce M; Ng, Raymond T; Sin, Don D

    2017-01-01

    There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80). These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD.

  1. Natriuretic Peptide and High-Sensitive Troponin T Concentrations Correlate with Effectiveness of Short-Term CPAP in Patients with Obstructive Sleep Apnea and Coronary Artery Disease

    PubMed Central

    Strehmel, Ralf; Valo, Misa; Teupe, Claudius

    2016-01-01

    The risk of cardiovascular complications is increased in patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the most effective way to treat clinically significant OSA. We hypothesized that the concentrations of the cardiac risk markers N-terminal brain natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TropT) correlate with the effectiveness of CPAP therapy in patients with OSA and coexisting coronary artery disease (CAD). Twenty-one patients with severe OSA and coexisting CAD (group 1) and 20 control patients with severe OSA alone (group 2) were treated with CPAP and monitored by laboratory-based polysomnography. NT-proBNP and hs-TropT levels were measured before and after CPAP. Apnea–hypopnea index (AHI) and oxygen desaturation were similar in both groups. In group 1, hs-TropT levels correlated with AHI and oxygen desaturation upon CPAP. Elevated NT-proBNP levels in group 1 were significantly reduced by CPAP. NT-proBNP levels correlated with AHI and showed negative correlation with ST-segment depression. No such correlations were found in group 2. CPAP has the potential to normalize elevated NT-proBNP serum levels in patients with severe OSA and coexisting CAD. Levels of NT-proBNP and hs-TropT correlated with AHI and oxygen desaturation. PMID:27980444

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

    PubMed

    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 < 0.001), and a cutoff value of 244.7 pg/mL yielded a sensitivity and specificity of 68.6 and 70.3 %, respectively. The area under the curve of the NT-proBNP for predicting Kawasaki disease was 0.763 (95 % CI 0.712-0.814).

  3. The O- and B-Type Stellar Population in W3: Beyond the High-Density Layer

    NASA Astrophysics Data System (ADS)

    Kiminki, Megan M.; Kim, Jinyoung Serena; Bagley, Micaela B.; Sherry, William H.; Rieke, George H.

    2015-11-01

    We present the first results from our survey of the star-forming complex W3, combining VRI photometry with multiobject spectroscopy to identify and characterize the high-mass stellar population across the region. With 79 new spectral classifications, we bring the total number of spectroscopically confirmed O- and B-type stars in W3 to 105. We find that the high-mass slope of the mass function in W3 is consistent with a Salpeter IMF, and that the extinction toward the region is best characterized by an RV of approximately 3.6. B-type stars are found to be more widely dispersed across the W3 giant molecular cloud (GMC) than previously realized: they are not confined to the high-density layer (HDL) created by the expansion of the neighboring W4 H ii region into the GMC. This broader B-type population suggests that star formation in W3 began spontaneously up to 8-10 Myr ago, although at a lower level than the more recent star formation episodes in the HDL. In addition, we describe a method of optimizing sky subtraction for fiber spectra in regions of strong and spatially variable nebular emission.

  4. THE O- AND B-TYPE STELLAR POPULATION IN W3: BEYOND THE HIGH-DENSITY LAYER

    SciTech Connect

    Kiminki, Megan M.; Kim, Jinyoung Serena; Bagley, Micaela B.; Rieke, George H.; Sherry, William H.

    2015-11-01

    We present the first results from our survey of the star-forming complex W3, combining VRI photometry with multiobject spectroscopy to identify and characterize the high-mass stellar population across the region. With 79 new spectral classifications, we bring the total number of spectroscopically confirmed O- and B-type stars in W3 to 105. We find that the high-mass slope of the mass function in W3 is consistent with a Salpeter IMF, and that the extinction toward the region is best characterized by an R{sub V} of approximately 3.6. B-type stars are found to be more widely dispersed across the W3 giant molecular cloud (GMC) than previously realized: they are not confined to the high-density layer (HDL) created by the expansion of the neighboring W4 H ii region into the GMC. This broader B-type population suggests that star formation in W3 began spontaneously up to 8–10 Myr ago, although at a lower level than the more recent star formation episodes in the HDL. In addition, we describe a method of optimizing sky subtraction for fiber spectra in regions of strong and spatially variable nebular emission.

  5. Recognition of subsets of the mammalian A/B-type core heterogeneous nuclear ribonucleoprotein polypeptides by novel autoantibodies.

    PubMed Central

    Dangli, A; Plomaritoglou, A; Boutou, E; Vassiliadou, N; Moutsopoulos, H M; Guialis, A

    1996-01-01

    The structurally related A/B-type core heterogeneous nuclear ribonucleoprotein (hnRNP) polypeptides of 34-39 kDa (A1, A2, B1 and B2) belong to a family of RNA-binding proteins that are major components of 40 S hnRNP complexes. By two-dimensional gel electrophoresis and peptide mapping analysis we compared each member of the A/B-type core proteins in the human and rat liver cells. This comparison revealed the unique presence in rat cells of major protein species, referred to as mBx polypeptides, that appeared as three charge isoforms at a position corresponding to the minor HeLa B1b protein spot. In addition, clear differences in the ratios of the A1 polypeptide to the A1b isoform were observed. The detection, in sera of patients with rheumatic autoimmune diseases, of two novel autoantibody specificities, one recognizing solely B2 protein and the second both the B2 and mBx polypeptides, helped to identify mBx proteins as new A/B-type hnRNP components, immunologically related to B2 protein. A common immunoreactive V8 protease peptide of approx. 17 kDa has been identified in B2 and mBx hnRNP polypeptides. mBx protein species are identified in cells of murine origin, and have a ubiquitous tissue distribution and developmental appearance. PMID:9003360

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

    PubMed Central

    Xia, Hui; Chen, Yao; Wu, Ke-Jia; Zhao, Hu; Xiong, Cheng-Liang; Huang, Dong-Hui

    2016-01-01

    C-type natriuretic peptide (CNP) is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B (NPR-B). Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods (such as immunolocalization, real time polymerase chain reaction and Western Blot), and then to evaluate the influence of CNP on sperm function in vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function. PMID:25926602

  7. Natriuretic peptides regulate the expression of tissue factor and PAI-1 in endothelial cells.

    PubMed

    Yoshizumi, M; Tsuji, H; Nishimura, H; Masuda, H; Kunieda, Y; Kawano, H; Kimura, S; Sugano, T; Kitamura, H; Nakagawa, K; Nakagawa, M

    1999-11-01

    In the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay. Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.

  8. The response of circulating brain natriuretic peptide to academic stress in college students.

    PubMed

    Amir, Offer; Sagiv, Moran; Eynon, Nir; Yamin, Chen; Rogowski, Ori; Gerzy, Yishay; Amir, Ruthie E

    2010-01-01

    Brain natriuretic peptide (BNP), a cardiac peptide, has been implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. The influence of academic stress on circulating concentration of the N-terminal fragment of BNP precursor (NT-proBNP), and in relation to the stress hormone (cortisol) response was studied in 170 college students undergoing major examinations. Just prior to the examination, we measured self-estimated stress level, systolic, and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma levels of cortisol, and NT-proBNP. These parameters were compared to the participants' baseline measurements, taken at the same hour of a different 'control day', without a major examination to induce stress. Hemodynamic variables (SBP, DBP, and HR) increased on the examination day compared with baseline values ( p < 0.001). Circulating cortisol concentration increased before examinations (+42%, p < 0.001). The response to stress was marked by a significant decrease in plasma NT-proBNP concentration (-40%, p < 0.001). We found in males a significant interaction between the cortisol elevation with examination stress and the NT-proBNP reduction ( p = 0.02). In response to academic stress, the plasma cortisol elevation was accompanied by a marked reduction in plasma NT-proBNP level. These data may indicate that mental stress entails an interface between the HPA axis and the peripheral natriuretic peptide system, leading to reciprocating changes in circulating levels of the corresponding hormones.

  9. Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs

    PubMed Central

    Pandey, Kailash N.

    2015-01-01

    The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed. PMID:26151885

  10. Protein electrophoresis - serum

    MedlinePlus

    ... Hemolysis Hyperimmunization Immunoelectrophoresis - blood Immunofixation blood test Liver disease Malignancy Malnutrition Nephrotic syndrome Rheumatoid arthritis Serum globulin electrophoresis Serum iron test Systemic lupus erythematosus ...

  11. The expression of atrial natriuretic peptide in the oviduct and its functions in pig spermatozoa.

    PubMed

    Zhang, Meijia; Hong, Haiyan; Zhou, Bo; Jin, Shiying; Wang, Chao; Fu, Maoyong; Wang, Songbo; Xia, Guoliang

    2006-06-01

    Locally synthesized atrial natriuretic peptide (ANP) and its receptors have been found in reproductive tissues of various mammals, and play an important role in the acrosome reaction of human sperm. The objective of the present study was to examine the expression of ANP and its receptors in pig spermatozoa and oviduct, and the effect of ANP on pig spermatozoa function. The expression of ANP and its receptors was analyzed by RT-PCR. Only natriuretic peptide receptors-A (NPRA) mRNA was detected in fresh sperm. While the levels of natriuretic peptide receptors-C (NPRC) mRNA were low with no obvious change among different oviductal phases, the levels of ANP mRNA were high in oviduct(OT)1 , OT3 and OT5, but were very low in OT2. On the other hand, the levels of NPRA mRNA were low in OT1 and OT2, increased in OT3 and reached a maximum in OT4 and OT5. Western blot analysis revealed that the level of ANP was high in OT1, decreased in OT2 and OT3, and arrived at the nadir in OT4 and OT5. The effect of ANP on spermatozoa function was studied by the acrosome reaction and IVF. Incubation with ANP for 1 h significantly induced acrosome reaction of preincubated spermatozoa, and maximal response of acrosome reaction (34.1 +/- 2.3%) was achieved at 1 nM ANP treatment. Both C-ANP-(4-23), a selective ligand of NPRC, and caffeine had no effect on the acrosome reaction. The stimulatory effect of ANP on acrosome reaction could be mimicked by the permeable cGMP analog, 8-Br-cGMP. ANP and caffeine had a similar effect on improving the oocytes penetration rate, polyspermy rate and the average number of sperm per penetrated oocyte. Also, ANP treatment had a similar effect on cleavage rate, blastocyst formation rate and the number of cells per blastocyst as that of caffeine treatment. The effects of ANP on the acrosome reaction and the parameters of oocyte penetration could be blocked by cGMP-dependent protein kinase (PKG) inhibitors KT5823 and/or Rp-8-pCPT-cGMPS. These results suggest that

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

    PubMed

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

    2014-07-18

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

  13. Blood levels and renal effects of atrial natriuretic peptide in normal man.

    PubMed Central

    Weidmann, P; Hasler, L; Gnädinger, M P; Lang, R E; Uehlinger, D E; Shaw, S; Rascher, W; Reubi, F C

    1986-01-01

    Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important

  14. Double N,B-Type Bidentate Boryl Ligands Enabling a Highly Active Iridium Catalyst for C-H Borylation.

    PubMed

    Wang, Guanghui; Xu, Liang; Li, Pengfei

    2015-07-01

    Boryl ligands hold promise in catalysis due to their very high electron-donating property. In this communication double N,B-type boryl anions were designed as bidentate ligands to promote an sp(2) C-H borylation reaction. A symmetric pyridine-containing tetraaminodiborane(4) compound (1) was readily prepared as the ligand precursor that could be used, in combination with [Ir(OMe)(COD)]2, to in situ generate a highly active catalyst for a broad range of (hetero)arene substrates including highly electron-rich and/or sterically hindered ones. This work provides the first example of a bidentate boryl ligand in supporting homogeneous organometallic catalysis.

  15. Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension

    NASA Astrophysics Data System (ADS)

    John, Simon W. M.; Krege, John H.; Oliver, Paula M.; Hagaman, John R.; Hodgin, Jeffrey B.; Pang, Stephen C.; Flynn, T. Geoffrey; Smithies, Oliver

    1995-02-01

    To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the proANP gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.

  16. Presence of immunoreactive atrial natriuretic peptide in follicular fluid, ovary and ovarian perfusates

    SciTech Connect

    Kim, Suhn Hee; Cho, Kyung Woo; Seul, Kyung Hwan; Ryu, Hoon; Koh, Gou Young )

    1989-01-01

    Immunoreactive atrial natriuretic peptide (ir-ANP) was measured in the follicular fluid of pig ovarian follicle, and rabbit ovarian homogenates and perfusates using a specific radioimmunoassay (RIA). Serial dilution curves made with the extracts of follicular fluid, ovarian homogenates and perfusates using Sep-Pak C18 cartridges were parallel with the RIA standard curve. On gel filtration chromatography and reverse phase HPLC, all extracted materials showed high and low molecular weight forms of ir-ANP. The amount of ir-ANP in rabbit ovary was 40.7{plus minus}0.39 pg/mg and that in follicular fluid of pig ovarian follicle was 18.88{plus minus}2.49 pg/ml.

  17. Atrial natriuretic factor (ANF) inhibits thyroid hormone secretion in the mouse

    SciTech Connect

    Ahren, B. )

    1990-01-01

    Recently, thyroid follicular cells were shown to exhibit atrial natriuretic factor (ANF)-like immunoreactivity and high affinity ANF receptors. In this study, we therefore examined the effects of synthetic rat ANF{sub 1-28} on basal and stimulated thyroid hormone secretion in the mouse, according to the McKenzie technique. Iodine deficient mice were pretreated with {sup 125}I and thyroxine. ANF (3 nmol/animal) was found to inhibit the increase in blood radioiodine levels that was induced by TSH or vasoactive intestinal polypeptide (VIP). Furthermore, ANF and norepinephrine additively inhibited the TSH-induced increase in blood radioiodine levels. It is concluded that ANF inhibits thyroid hormone secretion, which, therefore, might be locally regulated by intrathyroidal ANF.

  18. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats

    NASA Technical Reports Server (NTRS)

    Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.

    1995-01-01

    The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

  19. Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia

    SciTech Connect

    Lubbesmeyer, H.J.; Woodson, L.; Traber, L.D.; Flynn, J.T.; Herndon, D.N.; Traber, D.L. Thomas Jefferson Medical College, Philadelphia, PA Westfaelian Wilhelms Univ., Muenster )

    1988-04-01

    A bolus of Escherichia coli endotoxin (1.5 {mu}g/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

  20. Mechanisms underlying the diabetes-induced hyporeactivity of the rabbit carotid artery to atrial natriuretic peptide.

    PubMed

    Marrachelli, Vannina G; Miranda, Francisco J; Centeno, José M; Miranda, Ignacio; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Alborch, Enrique

    2011-03-01

    Atrial natriuretic peptide (ANP) plays an important role in the pathophysiology of the vascular complications in diabetes. The working hypothesis was that diabetes might modify the vascular actions of ANP in isolated rabbit carotid arteries and the mechanisms involved in these actions. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted carotid arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal increased the ANP-induced relaxation. Isatin inhibited the relaxation to ANP both in arteries with and without endothelium. Carotid arteries from diabetic rabbits showed a decreased natriuretic peptide receptor (NPR)-A expression and an enhanced NPR-C expression. Inhibition of NO-synthesis did not modify ANP-induced relaxation in control rabbits but inhibited it in diabetic rabbits. In arteries with endothelium indomethacin enhanced the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. In endothelium-denuded arteries indomethacin inhibited the relaxation to ANP in both groups of animals. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium inhibited the relaxation to ANP, and this inhibition was higher in diabetic than in control rabbits. These results suggest that diabetes produces hyporeactivity of the rabbit carotid artery to ANP by a mechanism that at least includes a reduced expression of NPR-A, an enhanced expression of NPR-C and a reduced participation of K(+)-channels. Furthermore, diabetes enhances endothelial NO release and diminishes the ratio thromboxane A(2)/prostacyclin. This increase of vasodilators could result from compensatory mechanisms counteracting the arterial hyporeactivity to ANP.

  1. Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Whitson, P. A.

    1993-01-01

    Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

  2. Two fission yeast B-type cyclins, cig2 and Cdc13, have different functions in mitosis.

    PubMed Central

    Bueno, A; Russell, P

    1993-01-01

    Cyclin B interacts with Cdc2 kinase to induce cell cycle events, particularly those of mitosis. The existence of cyclin B subtypes in several species has been known for some time, leading to speculation that key events of mitosis may be carried out by distinct functional classes of Cdc2/cyclin B. We report the discovery of cig2, a third B-type cyclin gene in Schizosaccharomyces pombe. Disruption of cig2 delays the onset of mitosis, to the degree that a cig2 null allele rescues mitotic catastrophe mutants, including those that are unable to carry out the inhibitory tyrosyl phosphorylation of Cdc2 kinase. Consistent with this, a cig2 null allele exhibits synthetic lethal interactions with cdc25ts and cdc2ts mutations. Mitotic phenotypes caused by disruption of cig2 are not reversed by increased production of Cdc13, the other fission yeast B-type cyclin that functions in mitosis. Likewise, a cdc13ts mutation is not rescued by increased gene dosage of cig2+. These data indicate that Cdc13 and Cig2 interact with Cdc2 to carry out different functions in mitosis. We suggest that some cyclin B subtypes found in other species, including humans, are also likely to have distinct, nonoverlapping functions in mitosis. Images PMID:8455610

  3. Block synthesis of A (type 2) and B (type 2) tetrasaccharides related to the human ABO blood group system.

    PubMed

    Ryzhov, Ivan M; Korchagina, Elena Yu; Popova, Inna S; Tyrtysh, Tatiana V; Paramonov, Alexander S; Bovin, Nicolai V

    2016-07-22

    Herein we report the synthesis of 3-aminopropyl glycosides of A (type 2) and B (type 2) tetrasaccharides via [3 + 1] block scheme. Peracetylated trichloroacetimidates of A and B trisaccharides were used as glycosyl donors. The well-known low reactivity of 4-OH group of N-acetyl-d-glucosamine forced us to test four glucosamine derivatives (3-Bz-1,6-anhydro-GlcNAc and 3-trifluoroacetamidopropyl β-glycosides of 3-Ac-6-Bn-GlcNAc, 3-Ac-6-Bn-GlcN3, and 3-Ac-6-Bn-GlcNAc2) to select the best glycosyl acceptor for the synthesis of type 2 tetrasaccharides. The desired tetrasacchrides were not isolated, when 3-trifluoroacetamidopropyl glycosyde of 3-Ac-6-Bn-GlcNAcβ was glycosylated. Glycosylation of 3-Bz-1,6-anhydro-GlcNAc derivative resulted in α-glycoside as a major product. High stereospecificity was achieved only in the synthesis of B (type 2) tetrasaccharide, when 3-trifluoroacetamidopropyl 3-Ac-6-Bn-GlcNAc2β was applied as the glycosyl acceptor (β/α 5:1), whereas glycosylation with trichloroacetimidate of A trisaccharide was not stereospecific (β/α 1.3:1). Glycosylation of 3-trifluoroacetamidopropyl glycoside of 3-Ac-6-Bn-GlcN3β with trichloroacetimidates of A and B trisaccharides provided the same stereochemical yield (β/α 1.5:1).

  4. Observation of atomic ordering of triple-period-A and -B type in GaAsBi

    SciTech Connect

    Wu, Mingjian Luna, Esperanza; Trampert, Achim; Puustinen, Janne; Guina, Mircea

    2014-07-28

    We report the observation of atomic ordering of triple-period (TP)-A and -B type in low temperature (LT) grown GaAsBi alloy using transmission electron microscopy (TEM). In addition to previous reports, where only TP-A ordering was identified in III-V alloys, here, we confirm by electron diffraction, high-resolution (HR) TEM, and HR Z-contrast scanning TEM that two ordering variants coexists for LT-GaAsBi. We find that the TP-A ordering variant dominates over the TP-B variant. TP-A domains extend over 50–100 nm (projected lateral width) and are of higher perfection compared to TP-B domains. HR Z-contrast scanning TEM on different domains reveals a variation in the Bi occupancy in the (111) planes with triple period sequence. Since the formation of ordered phases has been directly linked to the occurrence of specific surface reconstructions, our results suggest a correlation between the TP-A and B type domains and the multiple stability of n × 3 and 3 × n reconstructions on the (001) surface of GaAsBi under low temperature growth.

  5. Serum selenium assay following serum ferritin assay

    SciTech Connect

    Stevens, R.G.; Morris, J.S.; Hann, H.L.; Pulsipher, B.; Stahlhut, M.W.

    1986-08-01

    Stored serum samples can be an important research resource into the etiology of cancer. These sera cannot be replaced and should therefore be used to best advantage. In previous epidemiologic studies, only single serum constituents have been assayed in individual serum samples. For example, serum ferritin has been examined in samples stored for as long as 10 years at -20C for a possible relation with general mortality (1) and cancer death (2). Ferritin is the tissue iron-storage protein and is therefore subject to denaturation. Serum selenium has also been examined in relation to cancer risk in a prospective manner by using stored frozen serum samples (3, 4). The interactions of a variety of serum factors in relation to cancer risk would be a desirable research goal, except that the amounts of serum typically available in frozen serum banks are less than 1 ml. It was the purpose of this investigation to determine if a radioimmunoassay for ferritin affected a subsequent neutron activation assay for selenium on the same 0.1 ml serum sample.

  6. A- to B-Type Olivine Fabric Transitions Associated with Hydration, Dehydration and Shear Above the Farallon Flat Slab

    NASA Astrophysics Data System (ADS)

    Behr, W. M.; Smith, D.

    2014-12-01

    We investigate mantle rocks associated with hydration, dehydration and shear above the Farallon flat-slab at its contact with the base of North America. The rocks we focus on are ultramafic inclusions hosted within serpentinized ultramafic microbreccia diatremes of the Navajo Volcanic Field (New Mexico) that erupted to the surface at the waning stages of the Laramide orogeny. A large number of petrological and geochronological studies have pinpointed the origin of these rocks to the hydrated mantle wedge above the Farallon slab as well as tectonically eroded and entrained fragments of the plate interface. We combine petrological observations and EBSD measurements of olivine grainsize and LPO to examine the effects of hydration on olivine fabric development in different parts of the supra-subduction zone mantle. The rocks examined include weakly deformed to strongly foliated tectonites we interpret to represent partially hydrated fragments of the upper plate mantle; and mylonites and ultramylonites we interpret to represent deformed fragments of the plate interface. The rocks deformed at temperatures ranging from 500-900°C based on thermometry, and olivine compositions in some record heating just before incorporation in the diatreme mix. We observe the following: Tectonites exhibit A-type bulk olivine LPOs, but show transitions to B-type LPO in local, fine-grained, dynamically recrystallized regions associated with hydrous minerals. Mylonites and ultramylonites with stable chlorite and/or antigorite and recrystallized grainsizes of less than 10μm show strong B-type olivine LPOs. A single mylonite with recrystallized grainsizes of ~35μm shows evidence for prograde metamorphism and dehydration through the chlorite breakdown reaction at temperatures above ~770°C. It contains no hydrous minerals and shows a strong A-type olivine LPO. Together these rocks demonstrate a strong correlation between hydration under high stress conditions, and B-type olivine LPO

  7. Strategies for early detection of cardiotoxicities from anticancer therapy in adults: evolving imaging techniques and emerging serum biomarkers.

    PubMed

    Akhter, Nausheen; Murtagh, Gillian; Yancy, Clyde

    2015-01-01

    Significant advances have been made in detecting cancer therapeutics-related cardiac dysfunction with serum biomarkers, cardiovascular MRI, echocardiography and multi-modality approaches. Serum biomarkers, notably cardiac troponins and natriuretic peptides, have been evaluated for their prognostic ability in predicting left ventricular dysfunction. Imaging modalities, such as cardiovascular MRI and echocardiography, have been used for cardiac surveillance of patients with cancer undergoing chemotherapy. Developments in imaging, specifically myocardial deformation imaging, also known as strain, have been shown to be sensitive tools in detecting early changes in cardiac function. This review aims to synthesize the evidence that supports emerging serum biomarkers and complementary imaging modalities that continue to enhance the detection of cancer therapeutics-related cardiac dysfunction.

  8. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

    PubMed Central

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio

    2016-01-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  9. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.

    PubMed

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio; Saggio, Isabella

    2016-08-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence.

  10. Thermal expansion behavior of A- and B-type amylose crystals in the low-temperature region.

    PubMed

    Kobayashi, Kayoko; Kimura, Satoshi; Naito, Philip-Kunio; Togawa, Eiji; Wada, Masahisa

    2015-10-20

    The thermal expansion behaviors of A-type and B-type amylose crystals, which were prepared by recrystallization of short amylose chains synthesized by phosphorylase, were investigated using synchrotron X-ray powder diffraction between 100 and 300K. For both types of crystals, the room-temperature phase (RT phase), which is the usually observed phase, transitioned to a low-temperature phase (LT phase), on cooling. The phase transitions took place reversibly with rapid changes in the unit-cell parameters around 200-270K. The differences between the RT and LT phase were investigated using solid-state (13)C NMR spectroscopy, which revealed there were changes in molecular chain conformations. These results suggest that the phase transition of water molecules on the crystalline surfaces affects the thermal behavior and structure of polysaccharide crystals.

  11. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients.

    PubMed

    Zoccali, C; Mallamaci, F; Benedetto, F A; Tripepi, G; Parlongo, S; Cataliotti, A; Cutrupi, S; Giacone, G; Bellanuova, I; Cottini, E; Malatino, L S

    2001-07-01

    This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.

  12. Water deprivation enhances the inhibitory effect of natriuretic peptides on cAMP synthesis in rat renal glomeruli.

    PubMed

    Woodard, Geoffrey E; Li, Xiaohong; Rosado, Juan A

    2004-09-01

    This study investigates the effect of water deprivation on the expression of atrial natiruretic peptide (ANP)(1-28) binding sites in rat kidney. Water deprivation increased the B(max) of glomerular binding sites for ANP(1-28) and C-type natriuretic peptide (CNP)(1-22) without modifying their affinity, an effect that was prevented in the presence of C-atrial natriuretic factor (C-ANF), suggesting that natriuretic peptide receptor-C (NPR-C) binding sites might be enhanced. Our results indicate that ANP(1-28), CNP(1-22), and C-ANF inhibit cAMP synthesis directly stimulated by forskolin or by the physiological agonists histamine and 5-hydroxytryptamine. The inhibitory effect was found to be significantly greater in water-deprived rats than in controls. Our observations suggest that this effect must be attributed to the 67-kDa NPR-C-like protein, because the 67- and 77-kDa NPR-C-like proteins show high and low affinities for CNP(1-22), respectively, and the enhanced inhibitory effect of CNP on cAMP generation in water-deprived rats was detected at subnanomolar concentrations. In addition, using affinity cross-linking studies we have observed that water deprivation increases the expression of the 67-kDa NPR-C-like protein, and HS-142, which binds to NPR-A and the 77-kDa NPR-C-like but not the 67-kDa protein, reduced ligand internalization without affecting cAMP inhibition by ANP(1-28). Finally, we have found that ligand binding to the 67-kDa NPR-C-like protein is reduced by GTPgammaS, suggesting that this receptor is associated with a G protein in renal glomeruli. The enhanced inhibitory role of natriuretic peptides on cAMP synthesis induced by water deprivation may influence glomerular function in the rat kidney.

  13. [The interaction of atrial natriuretic peptide with other bioregulators of kidney function in chronic glomerulonephritis in children].

    PubMed

    Kucherenko, A G; Markov, Kh M; Zokirov, N Z; Naumova, V I

    1994-01-01

    A study was made of renin-angiotensin-aldosterone system activity and plasmic concentrations of atrial natriuretic peptide (NUP) as well as antidiuretic hormone in children with primary glomerulonephritis. A close relationship was established of these parameters in regulation of water-salt homeostasis. The above systems are involved in pathogenesis of childhood glomerulonephritis. This finding should be considered in development of pathogenetically validated therapy of glomerulonephritis, including introduction of synthetic NUP.

  14. Identification of a mouse B-type cyclin which exhibits developmentally regulated expression in the germ line

    NASA Technical Reports Server (NTRS)

    Chapman, D. L.; Wolgemuth, D. J.

    1992-01-01

    To begin to examine the function of cyclins in mammalian germ cells, we have screened an adult mouse testis cDNA library for the presence of B-type cyclins. We have isolated cDNAs that encode a murine B-type cyclin, which has been designated cycB1. cycB1 was shown to be expressed in several adult tissues and in the midgestation mouse embryo. In the adult tissues, the highest levels of cycB1 transcripts were seen in the testis and ovary, which contain germ cells at various stages of differentiation. The major transcripts corresponding to cycB1 are 1.7 and 2.5 kb, with the 1.7 kb species being the predominant testicular transcript and the 2.5 kb species more abundant in the ovary. Examination of cDNAs corresponding to the 2.5 kb and 1.7 kb mRNAs revealed that these transcripts encode identical proteins, differing only in the polyadenylation signal used and therefore in the length of their 3' untranslated regions. Northern blot and in situ hybridization analyses revealed that the predominant sites of cycB1 expression in the testis and ovary were in the germinal compartment, particularly in early round spermatids in the testis and growing oocytes in the ovary. Thus cycB1 is expressed in both meiotic and postmeiotic cells. This pattern of cycB1 expression further suggests that cycB1 may have different functions in the two cell types, only one of which correlates with progression of the cell cycle.

  15. Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

    PubMed Central

    Cody, R J; Atlas, S A; Laragh, J H; Kubo, S H; Covit, A B; Ryman, K S; Shaknovich, A; Pondolfino, K; Clark, M; Camargo, M J

    1986-01-01

    We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11 +/- 0.9 fmol/ml in NL and 71 +/- 9.9 in CHF (P less than 0.01); the latter with twofold right ventricular increment (P less than 0.05). In NL, ANF infusion of 0.10 microgram/kg per min (40 pmol/kg per min) induced increases (P less than 0.05) of absolute (from 160 +/- 23 to 725 +/- 198 mueq/min) and fractional (1-4%) sodium excretion, urine flow rate (from 10 +/- 1.6 to 20 +/- 2.6 ml/min), osmolar (from 3.2 +/- 0.6 to 6.8 +/- 1.2 ml/min) and free water (from 6.8 +/- 1.6 to 13.6 +/- 1.6 ml/min) clearances, and filtration fraction (from 20 +/- 1 to 26 +/- 2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P less than 0.01). Systolic blood pressure fell (from 112 +/- 3 to 104 +/- 5 mmHg, P less than 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11 +/- 1 to 7 +/- 1 mmHg, P less than 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P less than 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P less than 0.05) but not in CHF. Images PMID:2945832

  16. Usefulness of N-terminal pro-brain natriuretic peptide levels to predict success of weaning from intra-aortic balloon pumping.

    PubMed

    Tokita, Yukichi; Yamamoto, Takeshi; Sato, Naoki; Hosokawa, Yusuke; Munakata, Ryo; Akutsu, Koichi; Shimizu, Wataru; Tanaka, Keiji

    2014-09-15

    There is currently no reliable method of predicting the success of weaning from intra-aortic balloon pumping (IABP). The aim of this study was to investigate the ability of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level to predict the success of weaning from IABP. Consecutive patients scheduled for weaning from IABP were prospectively enrolled. NT-proBNP levels were measured at baseline (before the start of weaning) and cessation (just before cessation of IABP). Changes in NT-proBNP level between baseline and cessation were analyzed in 2 groups of patients: those who were successfully weaned and those who were not successfully weaned for any reason, including a decision to discontinue weaning, worsening of pulmonary edema after cessation of IABP, or unstable hemodynamics after cessation of IABP. A total of 30 patients were enrolled (mean age 66 ± 12 years, 16 men, 16 with acute myocardial infarctions, and 14 with acute exacerbation of chronic heart failure). Median (interquartile range) baseline NT-proBNP levels were not significantly different between the successful and unsuccessful weaning groups (4,200 [1,400 to 8,752] pg/ml vs (5,620 [2,035 to 13,950] pg/ml, p = 0.30). In the unsuccessful weaning group, the median NT-proBNP level was significantly higher at cessation (9,995 [2,920 to 15,100] pg/ml) than at baseline (p = 0.008). All patients with decreases in NT-proBNP level between baseline and cessation were successfully weaned from IABP. In conclusion, these results show that NT-proBNP levels were useful for predicting the success of weaning from IABP. If the NT-proBNP level increases during weaning from IABP, more intense management should be considered.

  17. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability.

    PubMed

    Jacob, Matthias; Saller, Thomas; Chappell, Daniel; Rehm, Markus; Welsch, Ulrich; Becker, Bernhard F

    2013-05-01

    Atrial natriuretic peptide (ANP) is a peptide hormone released from the cardiac atria during hypervolemia. Though named for its well-known renal effect, ANP has been demonstrated to acutely increase vascular permeability in vivo. Experimentally, this phenomenon was associated with a marked shedding of the endothelial glycocalyx, at least for supraphysiological intravascular concentrations. This study investigates the impact and mechanism of action of physiological doses of ANP and related peptides on the vascular barrier. In isolated guinea pig hearts, prepared and perfused in a modified Langendorff mode with and without the intravascular presence of the colloid hydroxyethyl starch (HES), we measured functional changes in vascular permeability and glycocalyx shedding related to intracoronary infusion of physiological concentrations of A-, B- and C-type natriuretic peptide (ANP, BNP and CNP). Significant coronary venous washout of glycocalyx constituents (syndecan-1 and heparan sulfate) was observed. As tested for ANP, this effect was positively related to the intracoronary concentration. Intravascular shedding of the glycocalyx was morphologically confirmed by electron microscopy. Also, functional vascular barrier competence decreased, as indicated by significant increases in transudate formation and HES extravasation. Ortho-phenanthroline, a non-specific inhibitor of matrix metalloproteases, was able to reduce ANP-induced glycocalyx shedding. These findings suggest participation of natriuretic peptides in pathophysiological processes like heart failure, inflammation or sepsis. Inhibition of metalloproteases might serve as a basis for future therapeutical options.

  18. Brain Natriuretic Peptide Stimulates Lipid Metabolism through Its Receptor NPR1 and the Glycerolipid Metabolism Pathway in Chicken Adipocytes.

    PubMed

    Huang, H Y; Zhao, G P; Liu, R R; Li, Q H; Zheng, M Q; Li, S F; Liang, Z; Zhao, Z H; Wen, J

    2015-11-03

    Brain natriuretic peptide (BNP) is related to lipid metabolism in mammals, but its effect and the molecular mechanisms underlying it in chickens are incompletely understood. We found that the level of natriuretic peptide precursor B (NPPB, which encodes BNP) mRNA expression in high-abdominal-fat chicken groups was significantly higher than that of low-abdominal-fat groups. Partial correlations indicated that changes in the weight of abdominal fat were positively correlated with NPPB mRNA expression level. In vitro, compared with the control group, preadipocytes with NPPB interference showed reduced levels of proliferation, differentiation, and glycerin in media. Treatments of cells with BNP led to enhanced proliferation and differentiation of cells and glycerin concentration, and mRNA expression of its receptor natriuretic peptide receptor 1 (NPR1) was upregulated significantly. In cells exposed to BNP, 482 differentially expressed genes were identified compared with controls without BNP. Four genes known to be related to lipid metabolism (diacylglycerol kinase; lipase, endothelial; 1-acylglycerol-3-phosphate O-acyltransferase 1; and 1-acylglycerol-3-phosphate O-acyltransferase 2) were enriched in the glycerolipid metabolism pathway and expressed differentially. In conclusion, BNP stimulates the proliferation, differentiation, and lipolysis of preadipocytes through upregulation of the levels of expression of its receptor NPR1 and key genes enriched in the glycerolipid metabolic pathway.

  19. The renal and vascular effects of central angiotensin II and atrial natriuretic factor in the anaesthetized rat.

    PubMed Central

    Al-Barazanji, K A; Balment, R J

    1990-01-01

    1. The interaction between atrial natriuretic factor (ANF) and angiotensin II (Ang II) within the brain to influence renal function and blood pressure was studied in Inactin-anaesthetized male Sprague-Dawley rats. 2. Central infusion of ANF produced a diuresis which was associated with a significant decrease in plasma arginine vasopressin (AVP) level. There was no change in sodium excretion rate over the 80 min of intracerebroventricular ANF infusion and ANF produced no detectable change in mean arterial blood pressure. 3. Central Ang II administration produced a significant decrease in urine flow, which was associated with elevated plasma AVP, an increase in sodium excretion and a rise in mean arterial blood pressure. 4. Combined ANF and Ang II infusion produced an antidiuresis, which was associated with increased plasma AVP concentration. Both the natriuretic and vasopressor actions of central Ang II were abolished when ANF was co-administered. 5. It is concluded that ANF and Ang II interact centrally; ANF antagonizes the pressor and natriuretic effects but not the antidiuretic effects of central Ang II. These data suggest the possibility of distinct and separate sites within the brain through which Ang II influences vasopressin release and renal sodium handling and elevates blood pressure. PMID:2143782

  20. [Usefulness of natriuretic peptide testing and Doppler echocardiography at bedside in the diagnosis of acute heart failure].

    PubMed

    Arques, S; Roux, E

    2016-11-01

    Acute heart failure is a common condition that leads to hospital admission, with important mortality and readmission rates. A prompt and accurate diagnosis of this condition by hospitalists is essential for an early and tailored medical management. The use of natriuretic peptide testing (BNP and NT-proBNP) through a two cut-point strategy is currently recommended as the first-line diagnostic complement to the initial clinical evaluation in the acute care setting. Transthoracic Doppler echocardiography is an other noninvasive method that can be used at bedside, especially in patients with intermediate, inconclusive natriuretic peptides levels. In this regard, left ventricular ejection fraction and several simple Doppler indexes (restrictive mitral filling pattern, spectral tissue Doppler E/e' ratio), have been validated in the emergency diagnosis of acute heart failure. The aim of the present review is to overview the respective contribution of natriuretic peptides and Doppler echocardiography at bedside to the diagnosis of acute heart failure in the acute care setting.

  1. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats

    PubMed Central

    Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-01-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways. PMID:26515144

  2. Serum herpes simplex antibodies

    MedlinePlus

    ... gov/ency/article/003352.htm Serum herpes simplex antibodies To use the sharing features on this page, please enable JavaScript. Serum herpes simplex antibodies is a blood test that looks for antibodies ...

  3. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  4. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    SciTech Connect

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  5. Serum sickness syndrome.

    PubMed

    Lin, R Y

    1986-01-01

    Numerous agents are known to cause serum sickness reactions. Although generally a benign disorder, serum sickness must be distinguished from various rheumatic and infectious disorders. The causative agent must be identified in order to avoid subsequent reactions. With the introduction of new drugs and biotechnically produced hormones and antibodies, new causes of serum sickness reactions are likely.

  6. Low-amplitude rotational modulation rather than pulsations in the CoRoT B-type supergiant HD 46769

    NASA Astrophysics Data System (ADS)

    Aerts, C.; Simón-Díaz, S.; Catala, C.; Neiner, C.; Briquet, M.; Castro, N.; Schmid, V. S.; Scardia, M.; Rainer, M.; Poretti, E.; Pápics, P. I.; Degroote, P.; Bloemen, S.; Østensen, R. H.; Auvergne, M.; Baglin, A.; Baudin, F.; Michel, E.; Samadi, R.

    2013-09-01

    Aims: We aim to detect and interpret photometric and spectroscopic variability of the bright CoRoT B-type supergiant target HD 46769 (V = 5.79). We also attempt to detect a magnetic field in the target. Methods: We analyse a 23-day oversampled CoRoT light curve after detrending and spectroscopic follow-up data using standard Fourier analysis and phase dispersion minimization methods. We determine the fundamental parameters of the star, as well as its abundances from the most prominent spectral lines. We perform a Monte Carlo analysis of spectropolarimetric data to obtain an upper limit of the polar magnetic field, assuming a dipole field. Results: In the CoRoT data, we detect a dominant period of 4.84 d with an amplitude of 87 ppm and some of its (sub-)multiples. Given the shape of the phase-folded light curve and the absence of binary motion, we interpret the dominant variability in terms of rotational modulation, with a rotation period of 9.69 d. Subtraction of the rotational modulation signal does not reveal any sign of pulsations. Our results are consistent with the absence of variability in the Hipparcos light curve. The spectroscopy leads to a projected rotational velocity of 72 ± 2 km s-1 and does not reveal periodic variability or the need to invoke macroturbulent line broadening. No signature of a magnetic field is detected in our data. A field stronger than ~500 G at the poles can be excluded, unless the possible non-detected field were more complex than dipolar. Conclusions: The absence of pulsations and macroturbulence of this evolved B-type supergiant is placed into the context of instability computations and of observed variability of evolved B-type stars. Based on CoRoT space-based photometric data; the CoRoT space mission was developed and operated by the French space agency CNES, with the participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain. Based on observations collected at La Silla Observatory, ESO

  7. Direct actin binding to A- and B-type lamin tails and actin filament bundling by the lamin A tail

    PubMed Central

    Simon, Dan N; Zastrow, Michael S

    2010-01-01

    Nuclear intermediate filament networks formed by A- and B-type lamins are major components of the nucleoskeleton. Lamins have growing links to human physiology and disease including Emery-Dreifuss muscular dystrophy (EDMD), lipodystrophy, cardiomyopathy, neuropathy, cerebellar disorders and segmental accelerated ‘aging’ syndromes. How lamins interact with other nucleoskeletal components, and even the identities of these other components, are open questions. Previous studies suggested lamins might bind actin. We report that the recombinant C-terminal tail domain of human A- and B-type lamins binds directly to purified actin in high-speed pelleting assays. This interaction maps to a conserved Actin Binding site (AB-1) comprising lamin A residues 461–536 in the Ig-fold domain, which are 54% identical in lamin B1. Two EDMD-causing missense mutations (R527P and L530P) in lamin A that are predicted to disrupt the Ig-fold, each reduced F-actin binding by ∼66%, whereas the surface-exposed lipodystrophy-causing R482Q mutation had no significant effect. The lamin A tail was unique among lamins in having a second actin-binding site (AB-2). This second site was mapped to lamin A tail residues 564–608, based on actin-binding results for the lamin C tail and internal deletions in the lamin A tail that cause Hutchinson-Gilford Progeria Syndrome (Δ35, Δ50) or restrictive dermopathy (Δ90). Supporting the presence of two actin-binding sites, recombinant precursor (unmodified) and mature lamin A tails (not C or B1 tails) each bundled F-actin in vitro: furthermore F-actin bundling was reduced 25–40% by the R527P, L530P, Δ35 and Δ50 mutations, and was abolished by Δ90. Unexpectedly, the mature lamin A tail bound F-actin significantly more efficiently than did the prelamin A tail; this suggested unmodified residues 647–664, unique to prelamin A, might auto-inhibit binding to actin (and potentially other partners). These biochemical results suggest direct mechanisms

  8. The Origin of Olivine B-Type Fabric in Naturally Deformed Peridotite: Insight from the Ronda Large-Scale Mantle Shear Zone (spain)

    NASA Astrophysics Data System (ADS)

    Précigout, J.; Hirth, G.

    2011-12-01

    Strain-induced olivine Lattice Preferred Orientation (LPO) mostly controls the propagation of seismic waves in the mantle. Hence, it strongly affects the imaging of mantle structures through analyzing of elastic waves coming from deep earthquakes (Ismaïl and Mainprice, 1998). Understanding the relationships between mantle deformation and olivine LPO is thus crucial to objectively interpret the deep mantle structures. Here, based on detailed documentation of olivine LPOs in the Ronda peridotite (southern Spain), we provide evidences of flow-normal a-axis LPO, i.e., B-type fabric, within a kilometer-scale ductile shear zone. This fabric occurs upon entering the shear zone and describes a progressive transition from A-type fabric (parallel-flow a-axis LPO) to B-type fabric. While B-type fabrics have been described from several localities, to our knowledge this is the first olivine fabric transition ever observed in naturally deformed peridotites. Furthermore, while the olivine fabric strength (Jindex) increases in the A-type fabric domain towards the center of the shear zone, the Jindex progressively decreases in the B-type fabric domain. Based on deformation experiments, A-type fabric occurs during high-temperature/low-stress deformation of anhydrous olivine aggregates (Jung and Karato, 2001). In contrast, the B-type fabrics have been observed under a wide range of conditions: 1) at high-temperature/low stress conditions in the presence of melt (Kohlstedt and Holtzman, 2009); 2) at high-stress in the presence of water (Jung and Karato, 2001); 3) under dry conditions at very high pressure (> 3 GPa; Jung et al., 2009); and 4) during diffusion-creep in the presence of orthopyroxene (Sundberg and Cooper, 2008). In our natural example, we conclude that the B-type fabric arises from enhancing diffusion creep at the expense of dislocation creep, because: 1) the B-type fabric is observed to overprint the typical fabric of anhydrous peridotite (A-type), 2) the Ronda

  9. Binding, internalization, and degradation of atrial natriuretic peptide in cultured vascular smooth muscle cells of rat

    SciTech Connect

    Hirata, Y.; Takata, S.; Tomita, M.; Takaichi, S.

    1985-11-15

    Binding, internalization, and degradation of /sup 125/I-labeled-rat atrial natriuretic peptide (rANP) were studied in cultured rat aortic vascular smooth muscle cells (VSMC). At 37 degrees C, /sup 125/I-labeled-rANP rapidly bound to VSMCs, but the cell-bound radioactivity rapidly decreased upon subsequent incubation, while the binding was slow at 4 degrees C, reaching to an apparent equilibrium after 6 hrs. The cell-bound /sup 125/I-labeled-rANP at 37 degrees C is rapidly dissociated from VSMC (t 1/2: approximately 40 min) with the appearance of degradaded product(s) of radioligand in the medium, whereas the degradation was minimal at 4 degrees C. This degradative process was blocked by inhibitors of metabolic energy production (azide, dinitrophenol), inhibitors of lysosomal cathepsins (leupeptin, pepstatin), and lysosomotropic agents (NH/sub 4/Cl, chloroquine, lidocaine, methylamine, dansylcadaverine), but not by inhibitors of serine or thiol proteases. /sup 125/I-labeled-rANP initially bound to the cell-surface was rapidly internalized, and delivered to lysosomal structures, which was confirmed by autoradiographic studies. These data indicate that rANP, after binding to the cell-surface receptors, is rapidly internalized into the cells through receptor-mediated endocytosis, and subsequently degradaded by lysosomal hydrolases.

  10. Analytical Issues with Natriuretic Peptides – has this been Overly Simplified?

    PubMed Central

    Katrukha, Alexey G.

    2016-01-01

    Natriuretic peptides (NPs) were first described as cardiac biomarkers more than two decades ago. Since that time, numerous studies have confirmed NPs’ diagnostic and prognostic utilities as biomarkers of myocardial function. However, we must now admit that despite the NPs’ relatively long period of use in clinical practice, our understanding of the biochemistry and the variety of circulating forms of NPs, as well as of their potential as biomarkers, remains far from being complete and comprehensive. The highly complex nature and wide diversity of circulating forms of NPs make their accurate measurements in plasma far more complex than initially believed. A highly simplistic view of the NPs’ use is that elevated values of NPs indicate the severity of heart failure and thus reflect the prognosis. However, as shown by a variety of studies, deep understanding of how the NP system works will be required for correct interpretation of test results in routine practice of cardiovascular disease. In this review, we summarize the recent advances in understanding of the complexity of the NP system and discuss related analytical issues, which open new horizons, as well as challenges for clinical diagnostics. PMID:27683533

  11. Regulation of endothelial cell shape and monolayer permeability by atrial natriuretic peptide

    SciTech Connect

    Lofton-Day, C.E.

    1989-01-01

    Atrial natriuretic peptide (ANP), considered to be an important regulator of intravascular fluid volume, binds specifically to receptors on endothelial cells. In this study, the role of ANP-specific binding was investigated by examining the effect of ANP on the morphology and macromolecular permeability of monolayer cultures of bovine aortic endothelial cells. ANP alone had no observable effect on the monolayers. However, incubation of monolayers with ANP antagonized thrombin- or glucose oxidase-induced cell shape changes and intercellular gap formation. ANP pretreatment also opposed the effect of thrombin and glucose oxidase on actin filament distribution as observed by rhodamine-phalloidin staining and digital image analysis of F0actin staining. In addition, ANP reversed cell shape changes and cytoskeletal alterations induced by thrombin treatment but did not reverse alternations induced by glucose oxidase treatment. ANP significantly reduced increases in monolayer permeability to albumin resulting from thrombin or glucose oxidases treatment. Thrombin caused a 2-fold increase in monolayer permeability to {sup 125}I-labeled albumin, which was abolished by 10{sup {minus}8}-10{sup {minus}6}M ANP pretreatment. Glucose oxidase caused similar increases in permeability and was inhibited by ANP at slightly shorter time periods.

  12. Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

    SciTech Connect

    Leitman, D.C.

    1988-01-01

    The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP.

  13. Atrial natriuretic factor in the impulse-conduction system of rat cardiac ventricles.

    PubMed

    Cantin, M; Thibault, G; Haile-Meskel, H; Ding, J; Milne, R W; Ballak, M; Charbonneau, C; Nemer, M; Drouin, J; Garcia, R

    1989-01-01

    A complex network of atrial natriuretic factor-producing cells has been delineated by biochemical and morphological techniques in the rat ventricular myocardium. The chordae tendineae spuriae (CTS; false tendons) contain ANF mRNA and the ANF propeptide (Asn 1-Tyr 126) as assessed by Northern blot analysis, high-pressure liquid chromatography and immunohisto- and -cytochemistry, using three different affinity-purified antibodies: monoclonal and polyclonal antibodies against C-terminal ANF (Arg 101-Tyr 126) and polyclonal antibodies against N-terminal ANF (Asp 11-Ala 37). Two types of cells harboring ANF-containing secretory granules constitute the CTS: the majority (Purkinje type I) have ultrastructural similarities with both atrial and classical Purkinje fibers. Purkinje type-II fibers resemble working ventricular cardiocytes. Both cell types harbor a large paranuclear Golgi complex. The subendocardial Purkinje network is also made up of these two cell types. In this location, Purkinje type-I fibers form cable-like structures while Purkinje type-II fibers are either located beneath the former or abut directly on the endocardium. The latter are not separated from adjacent working ventricular cardiocytes by connective tissue septa. Coronary arteries and arterioles, as in birds, are surrounded by a cushion of Purkinje type-II fibers which blend with the surrounding myocardium. These results indicate that, in the rat, the entire intraventricular conduction system is constituted of endocrine cells producing ANF.

  14. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension

    PubMed Central

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH. PMID:27419193

  15. Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

    SciTech Connect

    Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

    1987-01-01

    Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.

  16. Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

    PubMed

    Boeck, L; Eggimann, P; Smyrnios, N; Pargger, H; Thakkar, N; Siegemund, M; Marsch, S; Rakic, J; Tamm, M; Stolz, D

    2011-03-01

    Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

  17. The role of atrial natriuretic peptide (ANP) in cold-induced diuresis (CID)

    SciTech Connect

    Agnew, J.W.; Freund, B.J.; DuBose, D.A.; McKay, J.M.; Hashiro, G.M. Tripler Army Medical Center, Honolulu, HI )

    1991-03-11

    The hormonal control of cold-induced diuresis (CID) remains unresolved. This study investigated the role of ANP, plasma vasopressin (AVP), and aldosterone (ALDO) on CID. Four semi-nude men participated in a 210 min exposure to 15C and 29C air, on separate days. These subjects drank 300 mL of water and had an intravenous saline drip throughout both exposures to replace blood and insensible fluid losses. CID was observed in 15C but not in the 29C experiment, as indicated by a greater urine output. In 15C, atrial natriuretic peptide (ANP) increased after 90 min by 41% and remained elevated for 2 h relative to 29C. No differences were observed in AVP between 15C and 29C. In the 15C versus the 29C experiment, ALDO was approximately 37% lower at the pre, 15 and 90 min time periods. Mean arterial blood pressure was generally greater but only significant at 60 min during the 15C versus the 29C experiment. Urinary NA{sup +} excretion was elevated in 15C relative to 29C while no difference in K{sup +} excretion was observed. Although pressure effects may contribute, the observed natriuresis in the absence of a kaliuresis in the cold suggests a physiological role of ANP in CID.

  18. Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

    SciTech Connect

    Ogura, T.; Mitsui, T.; Yamamoto, I.; Katayama, E.; Ota, Z.; Ogawa, N.

    1987-01-19

    To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of (/sup 125/I)-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of (/sup 3/H)-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.

  19. Xanthomonas axonopodis pv. citri uses a plant natriuretic peptide-like protein to modify host homeostasis.

    PubMed

    Gottig, Natalia; Garavaglia, Betiana S; Daurelio, Lucas D; Valentine, Alex; Gehring, Chris; Orellano, Elena G; Ottado, Jorgelina

    2008-11-25

    Plant natriuretic peptides (PNPs) are a class of extracellular, systemically mobile molecules that elicit a number of plant responses important in homeostasis and growth. The bacterial citrus pathogen, Xanthomonas axonopodis pv. citri, also contains a gene encoding a PNP-like protein, XacPNP, that shares significant sequence similarity and identical domain organization with plant PNPs but has no homologues in other bacteria. We have expressed and purified XacPNP and demonstrated that the bacterial protein alters physiological responses including stomatal opening in plants. Although XacPNP is not expressed under standard nutrient rich culture conditions, it is strongly induced under conditions that mimic the nutrient poor intercellular apoplastic environment of leaves, as well as in infected tissue, suggesting that XacPNP transcription can respond to the host environment. To characterize the role of XacPNP during bacterial infection, we constructed a XacPNP deletion mutant. The lesions caused by this mutant were more necrotic than those observed with the wild-type, and bacterial cell death occurred earlier in the mutant. Moreover, when we expressed XacPNP in Xanthomonas axonopodis pv. vesicatoria, the transgenic bacteria caused less necrotic lesions in the host than the wild-type. In conclusion, we present evidence that a plant-like bacterial PNP can enable a plant pathogen to modify host responses to create conditions favorable to its own survival.

  20. Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Yancy, Clyde W.; Buckey, Jay C.; Lane, Lynda D.; Hargens, Alan R.; Blomqvist, C. G.

    1992-01-01

    A hypothesis is proposed that a temporal relationship exists between increases in cardiac filling pressure and plasma artrial natriuretic peptide (ANP) concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). To test the hypothesis, 30 ml/kg isotonic saline were infused in supine male subjects over 24 min and responses were monitored for 3 h postinfusion. Results show that at end infusion, mean arterial pressure (RAP), heart rate and plasma volume exhibited peak increases of 146, 23, and 27 percent, respectively. Mean plasma ANP and UV peaked (45 and 390 percent, respectively) at 30 min postinfusion. Most cardiovascular variables had returned toward control levels by 1 h postinfusion, and net reabsorption of extravascular fluid ensued. It is concluded that since ANP was not significantly increased until 30 min postinfusion, factors other than ANP initiate responses to intravascular fluid loading. These factors include increased vascular pressures, baroreceptor-mediated vasolidation, and hemodilution of plasma proteins. ANP is suggested to mediate, in part, the renal response to saline infusion.

  1. Modulation of RAAS-natriuretic peptides in the treatment of HF: Old guys and newcomers.

    PubMed

    Mollace, Vincenzo; Gliozzi, Micaela; Capuano, Annalisa; Rossi, Francesco

    2017-01-01

    The use of renin-angiotensin-aldosterone system (RAAS) inhibitors in the treatment of chronic heart failure (HF) and arterial hypertension is recommended by the European Society of Cardiology Guidelines on the basis of consolidated evidence supporting their efficacy in the development of such a disease. However, the high incidence of re-hospitalization and mortality in patients undergoing chronic HF, leads to the need for the development of novel RAAS inhibitors possessing a better pharmacokinetic/pharmacodynamics profile in approaching hemodynamic imbalance and myocardial dysfunction associated with the development of chronic HF. Here we summarize some of the recent advances in the area of RAAS-modulators, including novel renin inhibitors, mineralcorticoid receptor antagonists and novel AT1 and AT2-receptor modulators. In addition, the pharmacology of a new class of compounds which display both AT1-receptor blocking properties combined with inhibition of neprilysin, the vasopeptidase enzyme degradating natriuretic peptide (ARNi), will be reviewed, alongside with their impact in the pathophysiology of chronic HF.

  2. The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment

    PubMed Central

    Carnovali, Marino; Mastromarino, Vittoria

    2015-01-01

    After its discovery in the early 1980s, the natriuretic peptide (NP) system has been extensively characterized and its potential influence in the development and progression of heart failure (HF) has been investigated. HF is a syndrome characterized by the activation of different neurohormonal systems, predominantly the renin–angiotensin (Ang)–aldosterone system (RAAS) and the sympathetic nervous system (SNS), but also the NP system. Pharmacological interventions have been developed to counteract the neuroendocrine dysregulation, through the down modulation of RAAS with ACE (Ang-converting enzyme) inhibitors, ARBs (Ang receptor blockers) and mineralcorticoid antagonists and of SNS with β-blockers. In the last years, growing attention has been paid to the NP system. In the present review, we have summarized the current knowledge on the NP system, focusing on its role in HF and we provide an overview of the pharmacological attempts to modulate NP in HF: from the negative results of the study with neprilysin (NEP) inhibitors, alone or associated with an ACE inhibitor and vasopeptidase inhibitors, to the most recently and extremely encouraging results obtained with the new pharmacological class of Ang receptor and NEP inhibitor, currently defined ARNI (Ang receptor NEP inhibitor). Indeed, this new class of drugs to manage HF, supported by the recent results and a vast clinical development programme, may prompt a conceptual shift in the treatment of HF, moving from the inhibition of RAAS and SNS to a more integrated target to rebalance neurohormonal dysregulation in HF. PMID:26637405

  3. Studies of the penetration of the blood brain barrier by atrial natriuretic factor.

    PubMed

    Levin, E R; Frank, H J; Weber, M A; Ismail, M; Mills, S

    1987-09-30

    The atrial natriuretic factors (ANF) have been detected in various areas of the brain. To determine whether circulating blood borne ANF could contribute to the ANF content in the central nervous systems we examined the ability of ANF-99-126 or ANF-102-126 to penetrate the blood brain barrier. Carotid artery injections of [3H] inulin with [125I] ANF in anesthetized rabbits resulted in a comparably minimal brain uptake index (BUI) for each labeled substance as measured in cerebral cortex extracts. Injection of [3H] HOH and [125I] ANF resulted in a mean BUI in cortex of 4.9 +/- .6 (SEM)% for ANF relative to triated water; this low uptake was not significantly saturable. The BUI ratio for ANF/HOH in olfactory bulb was somewhat higher though still low, at 7.0 +/- 9%, possibly reflecting the high density of ANF receptors in this structure. Infusion of [125I] ANF into the carotid artery of anesthetized rabbits resulted in little radioactivity being detected in the cerebrospinal fluid. Infusion of unlabeled ANF, which raised plasma levels as high as 26.3 ng/ml, resulted in little change in CSF levels. Our results demonstrate that the uptake of ANF into the brain is minimal and supports the idea that local synthesis of ANF predominantly accounts for the brain pool of this peptide.

  4. Effect of prolonged high salt intake on atrial natriuretic factor's kinetics in rats

    SciTech Connect

    Widimsky, J.; Debinski, W.; Kuchel, O.; Buu, N.T.; Du Souich, P. )

    1990-05-01

    Plasma atrial natriuretic factor (ANF) paradoxically decreases after 5 weeks (but not after 3 weeks) of 8% NaCl intake in normotensive rats. As this phenomenon remains unaccounted for by changes in ANF production, we studied the disappearance of ({sup 125}I)ANF(99-126) from the circulation as an alternative explanation of plasma ANF decline. Following 5 weeks (but not 3 weeks) of an 8% NaCl diet, plasma concentrations of ({sup 125}I)ANF were significantly decreased and metabolic clearance rate and volume of distribution were increased compared to control rats fed a 0.8% NaCl diet. By studying ({sup 125}I)ANF tissue uptake we noted significantly greater peptide uptake after 5 weeks (but not after 3 weeks) of high salt consumption in several tissues. We hypothesize that prolonged (at least 5 weeks) 8% NaCl ingestion increases the density and/or affinity of ANF binding sites. These changes may be responsible for the previously observed decline in plasma ANF concentrations after a prolonged high salt intake.

  5. Urinary C-type natriuretic peptide: an emerging biomarker for heart failure and renal remodeling.

    PubMed

    Zakeri, Rosita; Burnett, John C; Sangaralingham, S Jeson

    2015-03-30

    The public health and economic burden of heart failure (HF) is staggering and the need for relevant pathophysiologic and clinical biomarkers to advance the field and improve HF therapy remains high. Renal dysfunction is common among HF patients and is associated with increased HF hospitalization and mortality. It is widely recognized that mechanisms contributing to HF pathogenesis include a complex bidirectional interaction between the kidney and heart, encompassed by the term cardiorenal syndrome (CRS). Among a new wave of urinary biomarkers germane to CRS, C-type natriuretic peptide (CNP) has emerged as an innovative biomarker of renal structural and functional impairment in HF and chronic renal disease states. CNP is a hormone, synthesized in the kidney, and is an important regulator of cell proliferation and organ fibrosis. Hypoxia, cytokines and fibrotic growth factors, which are inherent to both cardiac and renal remodeling processes, are among the recognized stimuli for CNP production and release. In this review we aim to highlight current knowledge regarding the biology and pathophysiological correlates of urinary CNP, and its potential clinical utility as a diagnostic and prognostic biomarker in HF and renal disease states.

  6. Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

    SciTech Connect

    Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.; Mantyh, P.W. )

    1988-09-01

    To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific binding of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.

  7. Atrial natriuretic factor: radioimmunoassay and effects on adrenal and pituitary glands

    SciTech Connect

    Gutkowska, J.; Horky, K.; Schiffrin, E.L.; Thibault, G.; Garcia, R.; De Lean, A.; Hamet, P.; Tremblay, J.; Anand-Srivastava, M.B.; Januszewicz, P.

    1986-06-01

    A simple and sensitive radioimmunoassay was developed for measurement of immunoreactive atrial natriuretic factor (IR-ANF) in rat and human plasma and in rat atria. The two atria contain about 20 ..mu..g ANF per rat. The right atrium contained 2.5 times more ANF than did the left. Ether anesthesia and morphine markedly increased IR-ANF in rat plasma. The concentration of IR-ANF in plasma of clinically normal human subjects was 65.3 +/- 2.5 pg/ml. Paroxysmal tachycardia and rapid atrial pacing significantly increased IR-ANF in human plasma. Two- to seven-fold higher concentrations were found in coronary sinus blood than in the peripheral circulation. In the plasma of rats and humans, circulating ANF is probably a small-molecular-weight peptide. ANF acts on the adrenal and the pituitary. ANF inhibits aldosterone secretion from rat zona glomerulosa and steroid secretion by bovine adrenal zona glomerulosa and fasciculata. ANF stimulated the basal secretion of arginine vasopressin (AVP) in vitro and inhibited KCl-stimulated release of AVP.

  8. Hypermethylation of brain natriuretic peptide gene is associated with the risk of rheumatic heart disease

    PubMed Central

    Li, Ni; Zheng, Dawei; Sun, Lebo; Shi, Huoshun; Zhu, Xiuying; Xu, Guodong; Wang, Qinning; Zhu, Caimin

    2016-01-01

    To investigate the contribution of brain natriuretic peptide (BNP) promoter DNA methylation to the risk of rheumatic heart disease (RHD) and the influence of warfarin anticoagulant therapy on BNP methylation levels for RHD patients after surgery. BNP methylation levels were determined by bisulfite pyrosequencing from plasma samples of RHD patients compared with healthy controls. Several factors influencing the RHD patients were included like age, smoking and cholesterol levels. A fragment of five CG sites (CpG1–5) in the promoter region of BNP gene was measured. BNP gene hypermethylation was found in CpG4 and CpG5 in RHD patients compared with non-RHD controls. A significant difference was also observed between RHD patients with long-term administration of warfarin and RHD patients who had recently undergone an operation. Moreover, single CpG4 and CpG5 analysis revealed a significant increase in methylation levels in men. BNP gene body hypermethylation is associated with the risk of RHD, and also influenced by the warfarin anticoagulant therapy of RHD patients after surgery, which could represent novel and promising targets for therapeutic development. PMID:27920275

  9. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  10. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension.

    PubMed

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH.

  11. Effects of posture and ageing on circulating atrial natriuretic peptide levels in man.

    PubMed

    Haller, B G; Züst, H; Shaw, S; Gnädinger, M P; Uehlinger, D E; Weidmann, P

    1987-10-01

    Possible influences of posture or age on plasma immunoreactive atrial natriuretic peptide (irANP) levels and potential correlates were assessed in 12 young (age +/- s.e.m. 24 +/- 1 year) and 12 elderly (63 +/- 8 year) healthy subjects on a liberal sodium intake. The groups did not differ significantly in their basal 24-h urinary sodium excretion (210 +/- 23 versus 180 +/- 15 mmol/l). However, plasma irANP was five- to ninefold higher in the elderly (P less than 0.05-0.01). Plasma irANP averaged 167 +/- 31 and 24 +/- 3 pg/ml in the elderly and young, respectively, during recumbency, fell (P less than 0.05) to 101 +/- 21 and 11 +/- 1 pg/ml, respectively, with upright posture, and rose (P less than 0.01) to 250 +/- 51 and 50 +/- 9 pg/ml, respectively, after intravenous (i.v.) loading with 0.9% saline (2.14 l in 3 h). Supine blood pressure (BP) and plasma norepinephrine tended to be higher while renin and aldosterone levels were lower (P less than 0.01) in the elderly; the three latter variables rose (P less than 0.001) with upright posture. These findings demonstrate that in normal humans, circulating irANP levels vary with posture and ageing. These changes may have potential physiological relevance and should be considered when interpreting plasma irANP levels in pathological conditions.

  12. Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction.

    PubMed

    Maeda, K; Tsutamoto, T; Wada, A; Mabuchi, N; Hayashi, M; Hisanaga, T; Kamijo, T; Kinoshita, M

    2000-08-01

    To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately 12 h after the attack) (group 1) and compared data with those obtained after 1 mo (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.

  13. Interpretation and Use of Natriuretic Peptides in Non-Congestive Heart Failure Settings

    PubMed Central

    Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

    2010-01-01

    Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article. PMID:20191004

  14. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    SciTech Connect

    Chartier, L.; Schiffrin, E.L.

    1987-04-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC/sub 50/) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC/sub 50/. In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated /sup 45/Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry.

  15. Improved HDDR processing route for production of anisotropic powder from sintered NdFeB type magnets

    NASA Astrophysics Data System (ADS)

    Sheridan, R. S.; Williams, A. J.; Harris, I. R.; Walton, A.

    2014-01-01

    The hydrogenation disproportionation desorption recombination (HDDR) process has been investigated as a possible means of producing bonded magnets from used NdFeB-type sintered magnets with compositions, Nd13.4Dy0.8Al0.7Nb0.3Fe78.5B6.3 and Nd12.5Dy1.8Al0.9Nb0.6Co5.0Fe72.8B6.4 (atomic%). It has been shown that by increasing the processing temperature, an increase in the equilibrium pressure for disproportionation and in the overall reaction time was observed. The magnetic properties of the lower Dy content magnet were affected significantly by the change in processing temperature with a peak in properties observed at 880 °C producing magnetic powder with a remanence of 1.08 (±0.02) T, a coercivity of 840 (±17) kA m-1, and a maximum energy product of 175 (±2.5) kJ m-3. Further work on magnets with a significantly higher Dy content has shown that simultaneous processing of sintered magnets with varying compositions can be achieved by increasing the hydrogen pressure, however a range of magnetic properties are produced depending on the initial compositions of the samples in the input feed.

  16. The unfolded protein response is a negative regulator of scavenger receptor class B, type I (SR-BI) expression.

    PubMed

    Eberhart, Tanja; Eigner, Karin; Filik, Yüksel; Fruhwürth, Stefanie; Stangl, Herbert; Röhrl, Clemens

    2016-10-21

    Scavenger receptor class B, type I (SR-BI) is the main receptor for high-density lipoprotein (HDL) and an emerging atheroprotective candidate. A central function of SR-BI is the delivery of HDL-derived cholesterol to the liver for subsequent excretion into the bile. Here, we investigated the regulation of SR-BI by the unfolded protein response (UPR), an adaptive mechanism induced by endoplasmic reticulum (ER) stress, which is frequently activated in metabolic disorders. We provide evidence that induction of acute ER stress by well-characterized chemical inducers leads to decreased SR-BI expression in hepatocyte-derived cell lines. This results in a functional reduction of selective lipid uptake from HDL. However, the regulation of SR-BI by ER stress is not a direct consequence of altered cellular cholesterol metabolism. Finally, we show that SR-BI down-regulation by the UPR might be a compensatory mechanism to provide partial adaption to ER stress. The observed down-regulation of SR-BI by ER stress in hepatic cells might contribute to the unfavorable effects of metabolic disorders on cholesterol homeostasis and cardiovascular diseases.

  17. The IACOB project . III. New observational clues to understand macroturbulent broadening in massive O- and B-type stars

    NASA Astrophysics Data System (ADS)

    Simón-Díaz, S.; Godart, M.; Castro, N.; Herrero, A.; Aerts, C.; Puls, J.; Telting, J.; Grassitelli, L.

    2017-01-01

    Context. The term macroturbulent broadening is commonly used to refer to a certain type of non-rotational broadening affecting the spectral line profiles of O- and B-type stars. It has been proposed to be a spectroscopic signature of the presence of stellar oscillations; however, we still lack a definitive confirmation of this hypothesis. Aims: We aim to provide new empirical clues about macroturbulent spectral line broadening in O- and B-type stars to evaluate its physical origin. Methods: We used high-resolution spectra of 430 stars with spectral types in the range O4 - B9 (all luminosity classes) compiled in the framework of the IACOB project. We characterized the line broadening of adequate diagnostic metal lines using a combined Fourier transform and goodness-of-fit technique. We performed a quantitative spectroscopic analysis of the whole sample using automatic tools coupled with a huge grid of fastwind models to determine their effective temperatures and gravities. We also incorporated quantitative information about line asymmetries into our observational description of the characteristics of the line profiles, and performed a comparison of the shape and type of line-profile variability found in a small sample of O stars and B supergiants with still undefined pulsational properties and B main-sequence stars with variable line profiles owing to a well-identified type of stellar oscillations or to the presence of spots in the stellar surface. Results: We present a homogeneous and statistically significant overview of the (single snapshot) line-broadening properties of stars in the whole O and B star domain. We find empirical evidence of the existence of various types of non-rotational broadening agents acting in the realm of massive stars. Even though all these additional sources of line-broadening could be quoted and quantified as a macroturbulent broadening from a practical point of view, their physical origin can be different. Contrarily to the early- to

  18. Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus.

    PubMed

    Woelke, Anna Lena; Wagner, Anke; Galstyan, Gegham; Meyer, Tim; Knapp, Ernst-Walter

    2014-11-04

    A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers.

  19. Microsatellite instability and B-type Raf proto-oncogene mutation in colorectal cancer: Clinicopathological characteristics and effects on survival

    PubMed Central

    Batur, Sebnem; Bakkaloglu, Dogu Vuralli; Kepil, Nuray; Erdamar, Sibel

    2016-01-01

    Prognostic significance of microsatellite instability (MSI) status and B-type Raf proto-oncogene (BRAF) mutation in colorectal cancer is controversial. The aim of this study was to examine the clinical and pathological characteristics associated with microsatellite stability and the effect of MSI and BRAF mutation on the survival of patients with colorectal cancer. The study included 145 colorectal cancer cases. All the patients were examined for DNA mismatch repair (MMR) proteins with an immunohistochemical method. Molecular assessment of MSI was available in a subset of 41 patients. In addition, BRAF mutation analysis was performed in 30 cases. Immunohistochemically, MMR deficiency was present in 28 (19.3%) patients. Female gender (p = 0.001), lesion size ≥5 cm (p = 0.013), Crohn-like response (p = 0.035), and right-sided localization (p < 0.001) were significantly more frequent among MMR-deficient patients. The overall survival was 44.1 ± 5.1 months (95% confidence interval [CI], 33.7-54.4). Multivariate analyses identified only high tumor grade as an independent predictor of poor overall survival: odd ratio, 6.7 (95% CI 2.1-21.7), p = 0.002. In the subset of patients with available BRAF assessment (n = 30), a negative BRAF status was associated with better survival when compared to a positive BRAF status (36.7 ± 2.1 vs. 34.1 ± 7.2 months, p = 0.048). The sensitivity and specificity of the immunohistochemical method in predicting positive MSI status, with the molecular method as a reference, were 85.7% (95% CI: 56.2%-97.5%) and 88.9% (95% CI: 69.7%-97.1%), respectively. BRAF appears to be a significant predictor of a worse outcome in patients with colorectal cancer. Further studies with a large spectrum of clinical and biological variables are warranted. PMID:27131021

  20. Water exit pathways and proton pumping mechanism in B-type cytochrome c oxidase from molecular dynamics simulations.

    PubMed

    Yang, Longhua; Skjevik, Åge A; Han Du, Wen-Ge; Noodleman, Louis; Walker, Ross C; Götz, Andreas W

    2016-09-01

    Cytochrome c oxidase (CcO) is a vital enzyme that catalyzes the reduction of molecular oxygen to water and pumps protons across mitochondrial and bacterial membranes. While proton uptake channels as well as water exit channels have been identified for A-type CcOs, the means by which water and protons exit B-type CcOs remain unclear. In this work, we investigate potential mechanisms for proton transport above the dinuclear center (DNC) in ba3-type CcO of Thermus thermophilus. Using long-time scale, all-atom molecular dynamics (MD) simulations for several relevant protonation states, we identify a potential mechanism for proton transport that involves propionate A of the active site heme a3 and residues Asp372, His376 and Glu126(II), with residue His376 acting as the proton-loading site. The proposed proton transport process involves a rotation of residue His376 and is in line with experimental findings. We also demonstrate how the strength of the salt bridge between residues Arg225 and Asp287 depends on the protonation state and that this salt bridge is unlikely to act as a simple electrostatic gate that prevents proton backflow. We identify two water exit pathways that connect the water pool above the DNC to the outer P-side of the membrane, which can potentially also act as proton exit transport pathways. Importantly, these water exit pathways can be blocked by narrowing the entrance channel between residues Gln151(II) and Arg449/Arg450 or by obstructing the entrance through a conformational change of residue Tyr136, respectively, both of which seem to be affected by protonation of residue His376.

  1. Oxygen abundance determination of B-type stars with the O I 7771-5 Å lines*

    NASA Astrophysics Data System (ADS)

    Takeda, Yoichi; Honda, Satoshi

    2016-06-01

    Oxygen abundances of 34 B-type stars in the effective temperature range of Teff ˜ 10000-28000 K with diversified rotational velocities (vesin i ˜ 0-250 km s-1) were determined from the O I triplet lines at 7771-5 Å, with an aim of examining whether this O I feature can be a reliable abundance indicator for such high-temperature stars including rapid rotators. It revealed that the required non-local thermodynamic equilibrium (LTE) abundance correction is distinctly large (ranging from ˜-0.6 dex to ˜-1.7 dex) and its consideration is indispensable. On the condition that the non-LTE effect is taken into account, this triplet is a useful O abundance indicator (with a precision of ≲ 0.2 dex) up to Teff ≲ 25000 K, since its total equivalent width is sufficiently large ( ≳ 200 mÅ). In contrast, it is not adequate for abundance derivation for stars at Teff ≳ 25000 K, where its strength rapidly drops down toward a hardly detectable level (except for sharp-lined stars) and its sensitivity to Teff or log g becomes considerably large. The resulting non-LTE oxygen abundances turned out to be almost normal (i.e., near-solar around ˜8.7-8.8 within ˜±0.2 dex) for most stars without any dependence upon projected rotational velocity as well as luminosity (or mass), which is consistent with the prediction of recent stellar evolution calculations.

  2. The neon content of nearby B-type stars and its implications for the solar model problem

    NASA Astrophysics Data System (ADS)

    Morel, T.; Butler, K.

    2008-08-01

    The recent downward revision of the solar photospheric abundances now leads to severe inconsistencies between the theoretical predictions for the internal structure of the Sun and the results of helioseismology. There have been claims that the solar neon abundance may be underestimated and that an increase in this poorly-known quantity could alleviate (or even completely solve) this problem. Early-type stars in the solar neighbourhood are well-suited to testing this hypothesis because they are the only stellar objects whose absolute neon abundance can be derived from the direct analysis of photospheric lines. Here we present a fully homogeneous NLTE abundance study of the optical Ne I and Ne II lines in a sample of 18 nearby, early B-type stars, which suggests log ɛ(Ne) = 7.97 ± 0.07 dex (on the scale in which log ɛ[H] = 12) for the present-day neon abundance of the local interstellar medium (ISM). Chemical evolution models of the Galaxy only predict a very small enrichment of the nearby interstellar gas in neon over the past 4.6 Gyr, implying that our estimate should be representative of the Sun at birth. Although higher by about 35% than the new recommended solar abundance, such a value appears insufficient by itself to restore the past agreement between the solar models and the helioseismological constraints. Appendices A and B are only available in electronic form at http://www.aanda.org Table [see full text] is also available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/487/307

  3. Group B, type III streptococcal cell wall: composition and structural aspects revealed through endo-N-acetylmuramidase-catalyzed hydrolysis.

    PubMed Central

    De Cueninck, B J; Shockman, G D; Swenson, R M

    1982-01-01

    Cell walls from a group B, type III streptococcus strain were prepared, purified by extraction with sodium dodecyl sulfate, and solubilized by the M-1 fraction of mutanolysin, an endo-N-acetylmuramidase obtained from Streptomyces globisporus. The lysate was resolved into three fractions by ion-exchange chromatography: a fraction containing peptidoglycan (PG) fragments, free of neutral and acidic sugars and of phosphate; a complex of PG fragments and group B-specific polysaccharide; and a complex of PG fragments and group B-specific polysaccharide and type III-specific polysaccharide. The PG-polysaccharide complexes were large and heterogeneous in molecular size. When subjected to base-catalyzed beta-elimination, both complexes were disintegrated, and polysaccharides and low-molecular-weight PG fragments could then be separated by gel filtration. The low-molecular-weight PG fragment-containing fraction contained muramic acid, glucosamine, alanine, lysine, glutamic acid, and serine in molar ratios (to lysine) of 0.92:0.98:3.01:1.00:1.00:0.05. Wall-derived, purified group polysaccharide contained rhamnose, galactose, glucosamine, and phosphorus in molar ratios (to galactose) of 5.03:1.00:1.00:1.05. It also contained an unidentified sugar. Wall-derived, purified type III polysaccharide contained galactose, glucosamine, glucose, and N-acetylneuraminic acid in molar ratios (to glucose) of 1.94:0.85:1.00:1.39. On a dry-weight basis, the whole wall lysate contained 19.8 and 20.6% of group and type polysaccharide, respectively. Neither glycerol nor ribitol was found, and all of the cell wall phosphorus was accounted for as polysaccharide, indicating the absence of a wall teichoic acid. PMID:7035367

  4. NLTE carbon abundance determination in selected A- and B-type stars and the interpretation of C I emission lines

    NASA Astrophysics Data System (ADS)

    Alexeeva, S. A.; Ryabchikova, T. A.; Mashonkina, L. I.

    2016-10-01

    We constructed a comprehensive model atom for C I-C II using the most up-to-date atomic data available and evaluated the non-local thermodynamic equilibrium (NLTE) line formation for C I and C II in classical 1D models representing the atmospheres of A- and late B-type stars. Our NLTE calculations predict the emission that appears at effective temperature of 9250 to 10 500 K depending on log g in the C I 8335, 9405 Å singlet lines and at Teff> 15 000 K (log g = 4) in the C I 9061-9111 Å, 9603-9658 Å triplet lines. A pre-requisite of the emission phenomenon is the overionization-recombination mechanism resulting in a depopulation of the lower levels of C I to a greater extent than the upper levels. Extra depopulation of the lower levels of the transitions corresponding to the near-infrared lines, is caused by photon loss in the UV lines C I 2479, 1930, and 1657 Å. We analysed the lines of C I and C II in Vega, HD 73666, Sirius, 21 Peg, π Cet, HD 22136, and ι Her taking advantage of their observed high-resolution spectra. The C I emission lines were detected in the four hottest stars, and they were well reproduced in our NLTE calculations. For each star, the mean NLTE abundances from lines of the two ionization stages, C I and C II, including the C I emission lines, were found to be consistent. We show that the predicted C I emission phenomenon depends strongly on whether accurate or approximate electron-impact excitation rates are applied.

  5. Theoretical study of the local charge compensation and spectroscopic properties of B-type carbonate defects in apatite

    NASA Astrophysics Data System (ADS)

    Yi, Haohao; Balan, Etienne; Gervais, Christel; Ségalen, Loïc; Blanchard, Marc; Lazzeri, Michele

    2014-05-01

    The structure and spectroscopic properties of selected models of B-type carbonate defects in apatite locally compensated by fluoride or hydroxyl ions are investigated using first-principles quantum mechanical calculations. Theoretical infrared absorption spectra and 13C, and 19F nuclear magnetic resonance chemical shifts are determined. Among the investigated models, only the clumped (CO3 2-, F-) defect, with the carbonate group close to the sloping face of the tetrahedral site and the F- ion at the remaining apex, corresponds to previous experimental observations performed on carbonate-fluorapatite samples. Although the substitution of hydroxyl by fluoride ions is commonly observed in minerals, the clumped (CO3 2-, OH-) defects are unlikely to occur in apatite, considering both their theoretical spectroscopic properties and relative stability. Anionic F- for OH- exchange between channel and B sites displays a preference of ~20 kJ/mol for the local charge compensation by fluoride ions at the B-site, pointing to a significantly different behavior of F- and OH- ions in the charge compensation mechanism. This difference is ascribed to the poor H-bond acceptor character of available oxygen atoms surrounding the apex of the tetrahedral site. The explicit calculation of the infrared absorption spectra of the defect models is also used to interpret the significant difference observed in the linewidth of the ν2 and ν3 CO3 infrared powder absorption bands of carbonated apatite samples. It is shown that for a concentration of 4.4 wt% of CO2, long-range electrostatic effects already significantly contribute to the broadening of the ν3 CO3 bands in apatite.

  6. The N/O Ratio in Early B-Type Main Sequence Stars as an Indicator of Their Evolution

    NASA Astrophysics Data System (ADS)

    Lyubimkov, L. S.

    2016-12-01

    It is shown that, in the case of early B-type main-sequence stars, of the three ratios N/C, C/O, and N/O which are regarded as indicators of stellar evolution, the ratio N/O is more reliable since it seems to be insensitive to overionization of the NII and OII ions. On the other hand, the N/C and C/O ratios, which include carbon, may contain systematic errors for stars with Teff > 18500 K because of neglected overionization of CII ions. The ratio N/O is studied in the atmospheres of 46 early main-sequence B stars. These values of N/O are examined as functions of the effective temperature, age, rotation speed, and mass of the stars. Most early B-stars in the main sequence are found to have [N/O] ≈ 0, which indicates that N/O varies little during the main sequence stage, and this result is independent of the basic parameters listed above. There are two explanations for the large number of stars with [N/O] ≈ 0 : it is predicted theoretically that for an initial rotation velocity V0 < 100 km/s, N/O varies little toward the end of the main sequence stage ([N/O] < 0.2) and observations show that most early main-sequence B-stars do actually have low initial rotation velocities V0. The few early main-sequence B-stars with higher [N/O] = 0.4-0.8 correspond to models with rotation velocities V0 = 200-300 km/s. This conclusion is consistent with earlier data for stars with the same masses in a later stage of evolution: the AFGsupergiant and bright giant stage.

  7. Testing the Wind-Shock Paradigm for B-Type Star X-Ray Production with θ Carinae

    NASA Astrophysics Data System (ADS)

    Doyle (Mizusawa), Trisha; Petit, Veronique; Held Cohen, David; Leutenegger, Maurice A.; Fullerton, Alexander W.

    2017-01-01

    We present Chandra X-ray grating spectroscopy of the B0.2V star, θ Carina. θ Car is in a critical transition region between the latest O-type and earliest B-type stars, where some stars are observed to have UV-determined wind densities much lower than theoretically expected. In general, X-ray emission in this low-density wind regime should be less prominent than O-star winds, but observations have shown a higher than expected production of X-ray emission from the winds of these stars; this hotter wind could explain the weak UV wind signature, but this might severely challenge predictions of radiatively driven wind theory. We measured the f/i ratio of several He-like ions and the widths of several He-like, H-like and Fe ions in the X-ray spectrum. The f/i ratio is a diagnostic of the radial location of the X-ray emitting plasma, which is modified by the distance to the UV-emitting stellar photosphere.Low flow velocity measured from the widths of the X-ray lines agree with a slower and lower density wind as compared to what is theoretically predicted from strong O-star wind theory. The measured widths are also consistent with other stars in the weak wind regime, β Cru, for example. The location of the X-ray emitting plasma is measured to be relatively close to the star, also consistent with a low-density wind and with other weak wind stars. We use θ Car to determine how low-density winds with a higher than expected X-ray production agrees or disagrees with the theory for radiatively-driven winds.

  8. Expression and regulation of scavenger receptor class B type 1 in the rat ovary and uterus during the estrous cycle.

    PubMed

    Wang, Yalei; Meng, Chenling; Wei, Quanwei; Shi, Fangxiong; Mao, Dagan

    2015-04-01

    Scavenger receptor class B type 1 (SR-B1) preferentially mediates the selective uptake of high density lipoprotein-cholesterol ester and the delivery of cholesterol for steroidogenesis. Although multiple analyses have investigated the function of SR-B1 in the liver, adrenal and ovary, its expression in rat ovary and uterus during the estrous cycle is lacking. In the present study, real-time PCR, western blot and immunohistochemistry (IHC) were used to investigate SR-B1 expression in the rat ovary and uterus during the estrous cycle. The results demonstrated that ovarian SR-B1 expression was in a stage-dependent manner, continuously increased from proestrus and kept elevated during metoestrus, while uterine SR-B1 expression decreased from proestrus to diestrus. To determine whether ovarian and uterine SR-B1 expression were affected by sex steroid hormones, immature rats were treated with 17 β-estradiol (E2), progesterone (P4), or their antagonists from postnatal days 24-26. Results showed that the levels of SR-B1 mRNA and protein were significantly up-regulated by E2 in both the ovary and uterus. IHC results showed that SR-B1 was primarily localized in the oocytes, theca internal cells (T-I) of follicles, interstitial cells (IC) as well as corpus luteum (CL), but not granulosa cells (GC) in the ovary during the estrous cycle. Uterine SR-B1 was highly expressed in the endometrial luminal epithelial cells (LEC) and glandular epithelial cells (GEC) as well as in the circular muscle (CM) cells, and weak staining in stromal cells (SC) through estrous cycle. Taken together, SR-B1 expression in the ovary and uterus across the estrous cycle demonstrate that SR-B1 may be involved in uterine function, follicular development as well as luteal function.

  9. C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression

    NASA Astrophysics Data System (ADS)

    Scotland, Ramona S.; Cohen, Marc; Foster, Paul; Lovell, Matthew; Mathur, Anthony; Ahluwalia, Amrita; Hobbs, Adrian J.

    2005-10-01

    The multifaceted process of immune cell recruitment to sites of tissue injury is key to the development of an inflammatory response and involved in the pathogenesis of numerous cardiovascular disorders. We recently identified C-type natriuretic peptide (CNP) as an important endothelium-derived mediator that regulates vascular tone and protects against myocardial ischemia/reperfusion injury. Herein, we investigated whether CNP inhibits leukocyte recruitment and platelet aggregation and thereby exerts a potential antiinflammatory influence on the blood vessel wall. We assessed the effects of CNP on leukocyte-endothelial cell interactions in mouse mesenteric postcapillary venules in vivo in animals with high basal leukocyte activation (endothelial nitric oxide synthase knockout mice, eNOS-/-) or under acute inflammatory conditions (induced by interleukin-1 or histamine). CNP suppressed basal leukocyte rolling in eNOS-/- mice in a rapid, reversible, and concentration-dependent manner. These effects of CNP were mimicked by the selective natriuretic peptide receptor-C agonist cANF4-23. CNP also suppressed leukocyte rolling induced by IL-1 or histamine, inhibited platelet-leukocyte interactions, and prevented thrombin-induced platelet aggregation of human blood. Furthermore, analysis of human umbilical vein endothelial cells, leukocytes, and platelets revealed that CNP selectively attenuates expression of P-selectin. Thus, CNP is a modulator of acute inflammation in the blood vessel wall characterized by leukocyte and platelet activation. These antiinflammatory effects appear to be mediated, at least in part, via suppression of P-selectin expression. These observations suggest that endothelial CNP might maintain an anti-atherogenic influence on the blood vessel wall and represent a target for therapeutic intervention in inflammatory cardiovascular disorders. endothelium | natriuretic peptide receptor type C | atherosclerosis | thrombosis

  10. Atrial natriuretic peptide and vasopressin-presence in the ciliary body of eye in the pig (sus domesticus).

    PubMed

    Valentino, B; Valentino, A; Lipari, L; Lipari, A; Farina, E

    2014-01-01

    The aqueous humor is produced in the ciliary body, therefore in this study we investigated the Atrial natriuretic peptide (ANP) and vasopressin (VP)-presence in the ciliary body of the pig eye since these peptide are involved in the homeostasis of body fluids. The results show ANP-presence in the epithelial cells and in the endothelial cells of the blood vessels and VP-presence in the epithelial cells, in the endothelium of canal of Schelmm and in the muscle cells of the blood vessels. These peptides might regulate the synthesis and the composition of the aqueous humor and regulate the hydrodynamic flow and haemodynamic flow of the blood.

  11. Vasotocin analogues with selective natriuretic, kaliuretic and antidiuretic effects in rats.

    PubMed

    Kutina, Anna V; Marina, Anna S; Shakhmatova, Elena I; Natochin, Yury V

    2013-08-10

    The aim of the present study was an investigation of mechanisms mediating selective effect of vasotocin analogues on water, sodium, and potassium excretion. We tested vasotocin analogues: Mpa(1)-vasotocin (dAVT), Mpa(1)-Arg(4)-vasotocin (dAAVT) and Mpa(1)-DArg(8)-vasotocin (dDAVT). The effects on water, sodium, and potassium transport were evaluated in experiments using normal and water-loaded Wistar rats. It was shown that all tested peptides exerted antidiuretic activity. Vasotocin and dAVT induced natriuresis and kaliuresis in rats. V1a agonist (Phe(2)-Ile(3)-Orn(8)-vasopressin) reproduced the renal effects of dAVT on sodium and potassium excretion but not on water reabsorption. dAAVT, dDAVT and V2 agonist (desmopressin) induced kaliuresis without any effect on sodium excretion. Natriuresis was associated with increase in cGMP excretion, whereas kaliuresis was correlated with rise of cAMP excretion. V1a antagonist (Pmp(1)-Tyr(Me)(2)-vasopressin) significantly reduced the dAVT-stimulated natriuresis and did not influence on urinary potassium excretion. V2 antagonist (Pmp(1)-DIle(2)-Ile(4)-vasopressin) significantly reduced the dAVT- and dAAVT-induced kaliuresis. It is assumed that effects of the nonapeptides on sodium and potassium transport are independent of their antidiuretic activity and mediated by different subtypes of V receptors (the V1a or V1a-like receptor for natriuretic effect and V2 or V2-like one for kaliuretic). In accordance to the data obtained, there is a possibility of selective regulation of renal water reabsorption and urinary sodium and potassium excretion with involvement of neurohypophysial hormones.

  12. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    PubMed

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium.

  13. Gene for the rat atrial natriuretic peptide is regulated by glucocorticoids in vitro.

    PubMed Central

    Gardner, D G; Gertz, B J; Deschepper, C F; Kim, D Y

    1988-01-01

    Glucocorticoids regulate the expression of the gene for atrial natriuretic peptide (ANP) in neonatal cardiocytes. Dexamethasone (Dex) increased cytoplasmic ANP mRNA levels and media ANP immunoreactivity in a dose-dependent fashion. These effects were not shared by the other classes of steroid hormones and were reversed by the glucocorticoid antagonist RU 38486. The effect on ANP mRNA levels resulted, at least in part, from enhanced transcription of the gene. Dex effected a two-fold increase in ANP gene activity assessed using a run-on transcription assay. The turnover of the ANP transcript was approximated using a standard pulse-chase technique. The half-life of the ANP mRNA was 18 h in hormone-free media. In the presence of Dex this half-life increased modestly to 30 h, although the increase relative to the control did not reach statistical significance. The effect of Dex at the level of the individual myocardial cell was assessed by in situ hybridization analysis using a specific [3H]cRNA probe. These studies demonstrated a significant level of ANP expression within a subpopulation of cells in the cultures. Exposure of the cells to Dex for 24 h did not recruit additional cells into the expressing pool (27.3% cells/high power field vs. 31.3% for the control) but did increase the level of expression (i.e., grain density) within individual cells. These findings indicate that glucocorticoids stimulate expression of the ANP gene directly at the level of the myocardial cell. This results predominantly from transcriptional activation in cells already expressing the gene rather than through recruitment of previously quiescent cells. Images PMID:2971674

  14. Thyrotropin modulates receptor-mediated processing of the atrial natriuretic peptide receptor in cultured thyroid cells

    SciTech Connect

    Tseng, Y.L.; Burman, K.D.; Lahiri, S.; Abdelrahim, M.M.; D'Avis, J.C.; Wartofsky, L. )

    1991-03-01

    In a prior study of atrial natriuretic peptide (ANP) binding to cultured thyroid cells, we reported that at 4 C, more than 95% of bound ANP is recovered on cell membranes, with negligible ANP internalization observed. Since ANP binding was inhibited by TSH, we have further studied TSH effects on postbinding ANP processing to determine whether this phenomenon reflects enhanced endocytosis of the ANP-receptor complex. An ANP chase study was initiated by binding (125I) ANP to thyroid cells at 4 C for 2 h, followed by incubation at 37 C. ANP processing was then traced by following 125I activity at various time intervals in three fractions: cell surface membranes, incubation medium, and inside the cells. Radioactivity released into medium represented processed ANP rather than ANP dissociated from surface membranes, since prebound (125I)ANP could not be competitively dissociated by a high concentration of ANP (1 mumol/L) at 37 C. Chase study results showed that prebound ANP quickly disappeared from cell membranes down to 34% by 30 min. Internalized ANP peaked at 10 min, with 21% of initial prebound ANP found inside the cells. At the same time, radioactivity recovered in incubation medium sharply increased between 10-30 min from 8% to 52%. Preincubation of cells with chloroquine (which blocks degradation of the ANP-receptor complex by inhibiting lysosomal hydrolase) caused a 146% increase in internalized (125I)ANP by 30 min (39% compared to 15% control), while medium radioactivity decreased from 52% to 16%, suggesting that processing of the receptor complex is mediated via lysosomal enzymes. In chase studies employing cells pretreated with chloroquine, TSH stimulated the internalization rate of ANP-receptor complex. By 30 min, TSH significantly reduced the membrane-bound ANP, and the decrease was inversely correlated to the increase in internalized radioactivity.

  15. Clonidine stimulates atrial natriuretic factor (ANF) release in water-deprived rats.

    PubMed

    Baranowska, B; Tremblay, J; Gutkowska, J

    1988-01-01

    To determine the effect of clonidine, an alpha 2-adrenergic agonist, on atrial natriuretic factor (ANF) release during water deprivation, plasma immunoreactive ANF (IR-ANF) arginine vasopressin, diuresis and natriuresis were measured in rats which had been deprived of water for 24 and 48 hr after intravenous (IV) administration of 50 micrograms clonidine. In normally-hydrated rats clonidine produced a marked elevation of plasma IR-ANF from 40.5 +/- 4.6 pg/ml to 1064 +/- 22 pg/ml (mean +/- SEM) and sodium excretion from 73.3 +/- 6.8 microEq to 723.4 +/- 62.3 microEq. Clonidine evoked an increase in plasma IR-ANF from 16.6 +/- 5.9 pg/ml to 229.5 +/- 60 pg/ml (mean +/- SEM) after 24 hr water deprivation and from 13.6 +/- 7.4 pg/ml to 104.8 +/- 21 pg/ml (mean +/- SEM) after 48 hr water deprivation. Clonidine did not induce any significant changes in vasopressin levels. During 24 hr and 48 hr water deprivation vasopressin rose from 3.1 +/- 0.3 pg/ml to 7.3 +/- 1.3 pg/ml and 8.4 +/- 0.6 pg/ml (mean +/- SEM), respectively. In normally-hydrated rats clonidine produced a marked diuresis and natriuresis. These effects and urinary cGMP excretion were significantly inhibited by anti-ANF antibodies. Clonidine caused a significant increase in urine output in 24 hr water-deprived rats but the response was markedly lower than that seen in normally-hydrated rats. In conclusion, clonidine stimulates ANF release both in normally-hydrated and water-deprived rats. The diuretic effect of clonidine appears to be related to ANF release but not to inhibition of vasopressin.

  16. Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

    PubMed Central

    Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Costa, María A.; Elesgaray, Rosana; Arranz, Cristina; Tomat, Analía L.

    2015-01-01

    Objective The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay. Results Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes. Conclusions Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes. PMID:25774801

  17. A Novel Bioassay for the Activity Determination of Therapeutic Human Brain Natriuretic Peptide (BNP)

    PubMed Central

    Yu, Lei; Rao, Chunming; Shi, Xinchang; Li, Yonghong; Gao, Kai; Li, Xuguang; Wang, Junzhi

    2012-01-01

    Background Recombinant human brain natriuretic peptide (rhBNP) is an important peptide-based therapeutic drug indicated for the treatment of acute heart failure. Accurate determination of the potency of therapeutic rhBNP is crucial for the safety and efficacy of the drug. The current bioassay involves use of rabbit aortic strips, with experiments being complicated and time-consuming and markedly variable in results. Animal-less methods with better precision and accuracy should be explored. We have therefore developed an alternative cell-based assay, which relies on the ability of BNP to induce cGMP production in HEK293 cells expressing BNP receptor guanylyl cyclase-A. Methodology/Principal Findings An alternative assay based on the measurement of BNP-induced cGMP production was developed. Specifically, the bioassay employs cells engineered to express BNP receptor guanylyl cyclase-A (GCA). Upon rhBNP stimulation, the levels of the second messager cGMP in these cells drastically increased and subsequently secreted into culture supernatants. The quantity of cGMP, which corresponds to the rhBNP activity, was determined using a competitive ELISA developed by us. Compared with the traditional assay, the novel cell-based assay demonstrated better reproducibility and precision. Conclusion/Significance The optimized cell-based assay is much simpler, more rapid and precise compared with the traditional assay using animal tissues. To our knowledge, this is the first report on a novel and viable alternative assay for rhBNP potency analysis. PMID:23185490

  18. Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium.

    PubMed Central

    Kinnunen, P.; Taskinen, T.; Järvinen, M.; Ruskoaho, H.

    1991-01-01

    1. To determine the cellular mechanisms of atrial natriuretic peptide (ANP) release from ventricular cardiomyocytes, the secretory and the cardiac effects of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase C activity in heart cells, were studied in isolated, perfused heart preparations from 2- and 21-month-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. TPA was added to the perfusion fluid for 30 min at a concentration of 46 nM after removal of atrial tissue. Additionally, atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP mRNA, the distribution of ANP within ventricles as well as the relative contribution of atria and ventricles in the release of ANP were studied. 2. Ventricular hypertrophy that gradually developed in hypertensive rats resulted in remarkable augmentation of ANP gene expression, as reflected by elevated levels of immunoreactive ANP and ANP mRNA. The total amount of IR-ANP in the ventricles of the SHR rats increased 41 fold and ANP mRNA levels 12.9 fold from the age of 2 to 21 months. At the age of 21 months, levels of IR-ANP and ANP mRNA in the ventricles of SHR rats were 5.4 fold and 3.7 fold higher, respectively, than in the normotensive WKY rats. Immunohistochemical studies demonstrated ANP granules within the hypertrophic ventricles of the old SHR rats, but not within normal ventricular tissue. 3. In isolated perfused heart preparations, the severely hypertrophied ventricular tissue of SHR rats after atrialectomy secreted more ANP into the perfusate than did the control hearts.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 PMID:1826618

  19. The relation between intraocular pressure change and plasma natriuretic peptide under simulated hypobaric conditions

    PubMed Central

    Karadag, Remzi; Sen, Ahmet; Yildirim, Nilgun; Basmak, Hikmet; Golemez, Haydar; Cakir, Erdinc; Akin, Ahmet

    2010-01-01

    Purpose: To ascertain whether the changes in intraocular pressure (IOP) that occur during hypobaric hypoxic exposure are related to plasma N-terminal pro-brain natriuretic peptide (BNP) levels. Materials and Methods: The study group comprised 26 healthy participants (all male, mean age 23.1 years). IOP was measured at local ground level, (792 m above sea level), then while in a chamber providing hypobaric hypoxic conditions (the subjects were exposed to a pressure equivalent to 9144 m for 1-3 min), and again after exit from the chamber. In each condition, the mean of three consecutive measurements of IOP was calculated for each eye. For BNP measurements, blood samples were drawn before the participants entered the chamber and just after they left the chamber. Results: IOP during hypobaric hypoxic exposure (18.00 ± 3.70 mmHg) was significantly greater than that before (15.66 ± 2.10 mmHg, P < 0.001) or after (16.10 ± 2.63 mmHg, P = 0.001) the exposure. IOP levels before and after the exposure were not significantly different (P = 0.136). Plasma BNP levels measured before and after exposure to hypobaric hypoxic conditions were not significantly different (P = 0.462). Conclusion: Plasma BNP levels did not change after short-term hypobaric hypoxic exposure, while the IOP increased. This increase may have been caused by some other systemic factors. As the hypobaric hypoxic conditions were reversed, IOP decreased to normal levels. PMID:20413920

  20. Atrial natriuretic peptide protects against Staphylococcus aureus-induced lung injury and endothelial barrier dysfunction

    PubMed Central

    Xing, Junjie; Moldobaeva, Nurgul

    2011-01-01

    Lung inflammation and alterations in endothelial cell (EC) permeability are key events to development of acute lung injury (ALI). Protective effects of atrial natriuretic peptide (ANP) have been shown against inflammatory signaling and endothelial barrier dysfunction induced by gram-negative bacterial wall liposaccharide. We hypothesized that ANP may possess more general protective effects and attenuate lung inflammation and EC barrier dysfunction by suppressing inflammatory cascades and barrier-disruptive mechanisms shared by gram-negative and gram-positive pathogens. C57BL/6J wild-type or ANP knockout mice (Nppa−/−) were treated with gram-positive bacterial cell wall compounds, Staphylococcus aureus-derived peptidoglycan (PepG) and/or lipoteichoic acid (LTA) (intratracheal, 2.5 mg/kg each), with or without ANP (intravenous, 2 μg/kg). In vitro, human pulmonary EC barrier properties were assessed by morphological analysis of gap formation and measurements of transendothelial electrical resistance. LTA and PepG markedly increased pulmonary EC permeability and activated p38 and ERK1/2 MAP kinases, NF-κB, and Rho/Rho kinase signaling. EC barrier dysfunction was further elevated upon combined LTA and PepG treatment, but abolished by ANP pretreatment. In vivo, LTA and PepG-induced accumulation of protein and cells in the bronchoalveolar lavage fluid, tissue neutrophil infiltration, and increased Evans blue extravasation in the lungs was significantly attenuated by intravenous injection of ANP. Accumulation of bronchoalveolar lavage markers of LTA/PepG-induced lung inflammation and barrier dysfunction was further augmented in ANP−/− mice and attenuated by exogenous ANP injection. These results strongly suggest a protective role of ANP in the in vitro and in vivo models of ALI associated with gram-positive infection. Thus ANP may have important implications in therapeutic strategies aimed at the treatment of sepsis and ALI-induced gram-positive bacterial

  1. C-type natriuretic peptide as a new regulator of food intake and energy expenditure.

    PubMed

    Inuzuka, Megumi; Tamura, Naohisa; Yamada, Nobuko; Katsuura, Goro; Oyamada, Naofumi; Taura, Daisuke; Sonoyama, Takuhiro; Fukunaga, Yasutomo; Ohinata, Kousaku; Sone, Masakatsu; Nakao, Kazuwa

    2010-08-01

    The physiological implication of C-type natriuretic peptide (CNP) including energy metabolism has not been elucidated, because of markedly short stature in CNP-null mice. In the present study we analyzed food intake and energy expenditure of CNP-null mice with chondrocyte-targeted CNP expression (CNP-Tg/Nppc(-/-) mice), in which marked skeletal dysplasia was rescued, to investigate the significance of CNP under minimal influences of skeletal phenotypes. In CNP-Tg/Nppc(-/-) mice, body weight and body fat ratio were reduced by 24% and 32%, respectively, at 20 wk of age, and decreases of blood glucose levels during insulin tolerance tests were 2-fold exaggerated at 17 wk of age, as compared with CNP-Tg/Nppc(+/+) mice. Urinary noradrenalin excretion of CNP-Tg/Nppc(-/-) mice was greater than that of CNP-Tg/Nppc(+/+) mice by 28%. In CNP-Tg/Nppc(-/-) mice, rectal temperature at 1600 h was higher by 1.1 C, and uncoupling protein-1 mRNA expression in the brown adipose tissue was 2-fold increased, which was canceled by propranolol administration, as compared with CNP-Tg/Nppc(+/+) mice. Oxygen consumption was significantly increased in CNP-Tg/Nppc(-/-) mice compared with that in CNP-Tg/Nppc(+/+) mice. Food intake of CNP-Tg/Nppc(-/-) mice upon ad libitum feeding and refeeding after 48 h starvation were reduced by 21% and 61%, respectively, as compared with CNP-Tg/Nppc(+/+) mice. This study unveiled a new aspect of CNP as a molecule regulating food intake and energy expenditure. Further analyses on precise mechanisms of CNP actions would lead to the better understanding of the significance of the CNP/guanylyl cyclase-B system in food intake and energy expenditure.

  2. Physiological factors of atrial natriuretic polypeptide release and its neural regulation in conscious dogs.

    PubMed

    Nishida, Y; Miyata, A; Morita, H; Hosomi, H

    1988-12-01

    We have examined physiological factors in atrial natriuretic polypeptide (ANP) release and whether or not the cardiac nerves control release of ANP. Two possible factors were tested, an increase in plasma sodium level (PNa) and an increase in atrial pressure. Injection of 1.0 or 2.0 mEq/kg of sodium ions elevated PNa by 5.3 +/- 0.3 or 7.3 +/- 0.4 mEq/L, respectively, but plasma ANP level (PANP) did not change. Infusion of 18 ml/kg of 3% Dextran-40 over 5 min increased mean left atrial pressure (MLAP) by 7.6 +/- 0.9 mmHg. PANP increased from 206 +/- 17 pg/ml to 260 +/- 25 pg/ml, which was not significant. PANP, corrected for hemodilution, significantly increased to 348 +/- 34 pg/ml. These results suggest that PNa increase does not promote ANP release, but that an atrial pressure increase does. This transient volume load did not induce full response of the ANP releasing system. A prolonged volume load for 45 min increased corrected PANP to 435 +/- 73 pg/ml. A close linear correlation was found between the increases in MLAP and PANP. These facts indicate that prolonged volume expansion is necessary to induce full response of the ANP releasing system. Complete cardiac denervation did not affect the tonic level of plasma ANP, volume expansion-induced increase in PANP, or the sensitivity of the ANP releasing system. Thus we conclude that the cardiac nerves do not control ANP release caused by volume expansion.

  3. Autoradiographic localization of atrial natriuretic peptide receptor subtypes in rat kidney

    SciTech Connect

    Brown, J.; Salas, S.P.; Singleton, A.; Polak, J.M. )

    1990-07-01

    The distribution of atrial natriuretic peptide (ANP) clearance receptors in rat kidney was investigated by in vitro autoradiography using des(Gln18,Ser19,Gly20,Leu21,Gly22)-ANP-(4- 23) (C-ANP) and 125I-Tyr0-ANP-(5-25) as relatively specific ligands of this receptor. Alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, outer medullary vasa recta bundles, and inner medulla. C-ANP (10 microM) inhibited greater than 60% of this glomerular binding but did not inhibit the binding of alpha-125I-ANP to medullary tissues. Alpha-125I-ANP also bound reversibly to the renal arteries up to the glomerulus. This arterial binding was only partly inhibited by 10 microM C-ANP. In the presence of 10 microM C-ANP, increasing concentrations of alpha-125I-ANP bound to a residue of glomerular sites with apparent dissociation constants of 0.82 +/- 0.16 to 2.73 +/- 1.20 nM at different cortical levels. 125I-Tyr0-ANP-(5-25) bound significantly to glomeruli and intrarenal arteries but not to vasa recta bundles or inner medulla. This glomerular binding also occurred with nanomolar dissociation constants. It was completely inhibited by 1 microM alpha-ANP and 10 microM C-ANP, but not by unrelated peptides such as gastrin. These results suggest that renal ANP clearance receptors are restricted in vivo to the glomeruli and renal arterial system of the rat.

  4. Synthesis, internalization, and localization of atrial natriuretic peptide in rat adrenal medulla

    SciTech Connect

    Morel, G.; Chabot, J.G.; Garcia-Caballero, T.; Gossard, F.; Dihl, F.; Belles-Isles, M.; Heisler, S.

    1988-07-01

    Some, though not all studies, have indicated that atrial natriuretic peptide (ANP) can bind to adrenal medullary cells. ANP-like immunoreactivity (ANP-LI) has also been identified in catecholamine-secreting cells. Together, these findings suggest that ANP may be taken up and/or synthesized in the adrenal medulla. The present study was designed to ascertain, by in situ hybridization, whether adrenal chromaffin cells could synthesize ANP, to define by an in vivo ultrastructural autoradiographic approach, whether ANP could, in fact, bind to rat adrenal medulla cells, to determine whether there was a cellular (noradrenaline (NA) vs. adrenaline (A)) selectivity in the binding process, and to establish whether extracellular (125I)ANP could be internalized by these cells. The cellular and subcellular distribution of endogenous ANP-LI was also investigated in both cell types by cryoultramicrotomy and immunocytochemical approaches. The in situ hybridization studies indicate the presence of mRNA to ANP in about 15% of adrenal medullary cells. Intravenous injection of (125I)ANP resulted in a 3-fold, preferential and specific radiolabeling of A-as compared to NA-containing cells. In A-containing cells, plasma membranes were significantly labeled 2 and 5 min post injection; cytoplasmic matrix, mitochondria, and secretory granules throughout the time course studied (1-30 min post injection). Lysosomes, rough endoplasmic reticulum, Golgi apparatus, and nuclei were not labeled. ANP-LI was identified in both NA- and A-containing cells; in the former, it was almost exclusively localized in secretory vesicles, in the latter it was detected in plasma membranes, cytoplasmic matrix, nuclear euchromatin, some mitochondria and relatively fewer granules than in NA-containing cells.

  5. Endothelial actions of atrial natriuretic peptide prevent pulmonary hypertension in mice.

    PubMed

    Werner, Franziska; Kojonazarov, Baktybek; Gaßner, Birgit; Abeßer, Marco; Schuh, Kai; Völker, Katharina; Baba, Hideo A; Dahal, Bhola K; Schermuly, Ralph T; Kuhn, Michaela

    2016-03-01

    The cardiac hormone atrial natriuretic peptide (ANP) regulates systemic and pulmonary arterial blood pressure by activation of its cyclic GMP-producing guanylyl cyclase-A (GC-A) receptor. In the lung, these hypotensive effects were mainly attributed to smooth muscle-mediated vasodilatation. It is unknown whether pulmonary endothelial cells participate in the homeostatic actions of ANP. Therefore, we analyzed GC-A/cGMP signalling in lung endothelial cells and the cause and functional impact of lung endothelial GC-A dysfunction. Western blot and cGMP determinations showed that cultured human and murine pulmonary endothelial cells exhibit prominent GC-A expression and activity which were markedly blunted by hypoxia, a condition known to trigger pulmonary hypertension (PH). To elucidate the consequences of impaired endothelial ANP signalling, we studied mice with genetic endothelial cell-restricted ablation of the GC-A receptor (EC GC-A KO). Notably, EC GC-A KO mice exhibit PH already under resting, normoxic conditions, with enhanced muscularization of small arteries and perivascular infiltration of inflammatory cells. These alterations were aggravated on exposure of mice to chronic hypoxia. Lung endothelial GC-A dysfunction was associated with enhanced expression of angiotensin converting enzyme (ACE) and increased pulmonary levels of Angiotensin II. Angiotensin II/AT1-blockade with losartan reversed pulmonary vascular remodelling and perivascular inflammation of EC GC-A KO mice, and prevented their increment by chronic hypoxia. This experimental study indicates that endothelial effects of ANP are critical to prevent pulmonary vascular remodelling and PH. Chronic endothelial ANP/GC-A dysfunction, e.g. provoked by hypoxia, is associated with activation of the ACE-angiotensin pathway in the lung and PH.

  6. Plant natriuretic peptides induce proteins diagnostic for an adaptive response to stress

    PubMed Central

    Turek, Ilona; Marondedze, Claudius; Wheeler, Janet I.; Gehring, Chris; Irving, Helen R.

    2014-01-01

    In plants, structural and physiological evidence has suggested the presence of biologically active natriuretic peptides (PNPs). PNPs are secreted into the apoplast, are systemically mobile and elicit a range of responses signaling via cGMP. The PNP-dependent responses include tissue specific modifications of cation transport and changes in stomatal conductance and the photosynthetic rate. PNP also has a critical role in host defense responses. Surprisingly, PNP-homologs are produced by several plant pathogens during host colonization suppressing host defense responses. Here we show that a synthetic peptide representing the biologically active fragment of the Arabidopsis thaliana PNP (AtPNP-A) induces the production of reactive oxygen species in suspension-cultured A. thaliana (Col-0) cells. To identify proteins whose expression changes in an AtPNP-A dependent manner, we undertook a quantitative proteomic approach, employing tandem mass tag (TMT) labeling, to reveal temporal responses of suspension-cultured cells to 1 nM and 10 pM PNP at two different time-points post-treatment. Both concentrations yield a distinct differential proteome signature. Since only the higher (1 nM) concentration induces a ROS response, we conclude that the proteome response at the lower concentration reflects a ROS independent response. Furthermore, treatment with 1 nM PNP results in an over-representation of the gene ontology (GO) terms “oxidation-reduction process,” “translation” and “response to salt stress” and this is consistent with a role of AtPNP-A in the adaptation to environmental stress conditions. PMID:25505478

  7. Order-disorder transition in B-type Cu2ZnSnS4 and limitations of ordering through thermal treatments

    NASA Astrophysics Data System (ADS)

    Rudisch, Katharina; Ren, Yi; Platzer-Björkman, Charlotte; Scragg, Jonathan

    2016-06-01

    B-type Cu2ZnSnS4 (CZTS) thin films with varying degrees of cation order were produced and examined with resonant Raman spectroscopy. Simulations based on Vineyard's theory of order allowed kinetic analysis of the final degree of order after the applied thermal treatments. Combining the results from the simulations and the resonant Raman spectra, the kinetic parameters within the Vineyard model for the order-disorder transition in B-type CZTS were determined, as well as a method which allows quantification of the degree of order based on resonant Raman spectra. The knowledge gained about the order-disorder transition in B-type CZTS allowed the prediction of a best practice thermal treatment for high ordering. This further leads to awareness about practical limits of thermal treatments regarding the cation ordering in B-type CZTS, and suggests that such treatments are not able to produce the high cation order necessary to sufficiently reduce detrimental potential fluctuations.

  8. The B-type channel is a major route for iron entry into the ferroxidase center and central cavity of bacterioferritin

    SciTech Connect

    Wong, Steve G.; Grigg, Jason C.; Le Brun, Nick E.; Moore, Geoffrey R.; Murphy, Michael E. P.; Mauk, A. Grant

    2014-12-15

    Bacterioferritin is a bacterial iron storage and detoxification protein that is capable of forming a ferric oxyhydroxide mineral core within its central cavity. To do this, iron must traverse the bacterioferritin protein shell, which is expected to occur through one or more of the channels through the shell identified by structural studies. The size and negative electrostatic potential of the 24 B-type channels suggest that they could provide a route for iron into bacterioferritin. Residues at the B-type channel (Asn-34, Glu-66, Asp-132, and Asp-139) of E. coli bacterioferritin were substituted to determine if they are important for iron core formation. A significant decrease in the rates of initial oxidation of Fe(II) at the ferroxidase center and subsequent iron mineralization was observed for the D132F variant. The crystal structure of this variant shows that substitution of residue 132 with phenylalanine caused a steric blockage of the B-type channel and no other material structural perturbation. Here, we conclude that the B-type channel is a major route for iron entry into both the ferroxidase center and the iron storage cavity of bacterioferritin.

  9. The B-type channel is a major route for iron entry into the ferroxidase center and central cavity of bacterioferritin

    DOE PAGES

    Wong, Steve G.; Grigg, Jason C.; Le Brun, Nick E.; ...

    2014-12-15

    Bacterioferritin is a bacterial iron storage and detoxification protein that is capable of forming a ferric oxyhydroxide mineral core within its central cavity. To do this, iron must traverse the bacterioferritin protein shell, which is expected to occur through one or more of the channels through the shell identified by structural studies. The size and negative electrostatic potential of the 24 B-type channels suggest that they could provide a route for iron into bacterioferritin. Residues at the B-type channel (Asn-34, Glu-66, Asp-132, and Asp-139) of E. coli bacterioferritin were substituted to determine if they are important for iron core formation.more » A significant decrease in the rates of initial oxidation of Fe(II) at the ferroxidase center and subsequent iron mineralization was observed for the D132F variant. The crystal structure of this variant shows that substitution of residue 132 with phenylalanine caused a steric blockage of the B-type channel and no other material structural perturbation. Here, we conclude that the B-type channel is a major route for iron entry into both the ferroxidase center and the iron storage cavity of bacterioferritin.« less

  10. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte.

    PubMed

    Reboul, Emmanuelle; Klein, Alexis; Bietrix, Florence; Gleize, Béatrice; Malezet-Desmoulins, Christiane; Schneider, Martina; Margotat, Alain; Lagrost, Laurent; Collet, Xavier; Borel, Patrick

    2006-02-24

    Although cellular uptake of vitamin E was initially described as a passive process, recent studies in the liver and brain have shown that SR-BI (scavenger receptor class B type I) is involved in this phenomenon. As SR-BI is expressed at high levels in the intestine, the present study addressed the involvement of SR-BI in vitamin E trafficking across enterocytes. Apical uptake and efflux of the main dietary forms of vitamin E were examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium. (R,R,R)-gamma-tocopherol bioavailability was compared between wild-type mice and mice overexpressing SR-BI in the intestine. The effect of vitamin E on enterocyte SR-BI mRNA levels was measured by real-time quantitative reverse transcription-PCR. Concentration-dependent curves for vitamin E uptake were similar for (R,R,R)-alpha-, (R,R,R)-gamma-, and dl-alpha-tocopherol. (R,R,R)-alpha-tocopherol transport was dependent on incubation temperature, with a 60% reduction in absorption at 4 degrees C compared with 37 degrees C (p < 0.05). Vitamin E flux in enterocytes was directed from the apical to the basal side, with a relative 10-fold reduction in the transfer process when measured in the opposite direction (p < 0.05). Co-incubation with cholesterol, gamma-tocopherol, or lutein significantly impaired alpha-tocopherol absorption. Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 80% of vitamin E uptake and up to 30% of apical vitamin E efflux (p < 0.05), and similar results were obtained for (R,R,R)-gamma-tocopherol. SR-BI mRNA levels were not significantly modified after a 24-h incubation of Caco-2 cells with vitamin E. Finally, (R,R,R)-gamma-tocopherol bioavailability was 2.7-fold higher in mice overexpressing SR-BI than in wild-type mice (p < 0.05). The present data show for the first time that vitamin E intestinal absorption is, at least in part, mediated by SR-BI.

  11. Diuretic and Natriuretic Effects of Dipeptidyl Peptidase-4 Inhibitor Teneligliptin: The Contribution of Glucagon-like Peptide-1.

    PubMed

    Moroi, Masao; Kubota, Tetsuya

    2015-08-01

    Glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are antidiabetic agents; however, their mechanisms of action are different. GLP-1R and DPP-4 are also expressed in the renal proximal tubular brush border, where they regulate Na reabsorption. We investigated whether the DPP-4 inhibitor, teneligliptin, has diuretic and natriuretic effects and whether these are associated with the stimulation of the GLP-1R in rats. Oral administration of teneligliptin resulted in a reduction of plasma DPP-4 activity over 6 hours, as well as an induction of diuresis and natriuresis. Although teneligliptin did not change the increase in blood glucose levels by glucose loading, percentage of urine volume and Na/K ratio with teneligliptin to vehicle were augmented by glucose loading. Peak levels of plasma GLP-1 did not change after oral administration of teneligliptin when glucose was not loaded but increased at least 2-fold with glucose loading. Furthermore, the natriuretic effect of teneligliptin was inhibited by the GLP-1R antagonist, exendin9-39, whereas the diuresis was not affected. These results suggest that the mechanism of natriuresis was different from that of diuresis, and the natriuresis is associated with the stimulation of GLP-1R. There may be mechanistic differences in DPP-4 inhibition between diuresis and natriuresis.

  12. Natriuretic Peptide Receptor B modulates the proliferation of the cardiac cells expressing the Stem Cell Antigen-1

    PubMed Central

    Rignault-Clerc, Stéphanie; Bielmann, Christelle; Liaudet, Lucas; Waeber, Bernard; Feihl, François; Rosenblatt-Velin, Nathalie

    2017-01-01

    Brain Natriuretic Peptide (BNP) injections in adult “healthy” or infarcted mice led to increased number of non-myocyte cells (NMCs) expressing the nuclear transcription factor Nkx2.5. The aim of this study was to identify the nature of the cells able to respond to BNP as well as the signaling pathway involved. BNP treatment of neonatal mouse NMCs stimulated Sca-1+ cell proliferation. The Sca-1+ cells were characterized as being a mixed cell population involving fibroblasts and multipotent precursor cells. Thus, BNP treatment led also to increased number of Sca-1+ cells expressing Nkx2.5, in Sca-1+ cell cultures in vitro and in vivo, in the hearts of neonatal and adult infarcted mice. Whereas BNP induced Sca-1+ cell proliferation via NPR-B receptor and protein kinase G activation, CNP stimulated Sca-1+ cell proliferation via NPR-B and a PKG-independent mechanism. We highlighted here a new role for the natriuretic peptide receptor B which was identified as a target able to modulate the proliferation of the Sca-1+ cells. The involvement of NPR-B signaling in heart regeneration has, however, to be further investigated. PMID:28181511

  13. C-type natriuretic peptide-modified lipid vesicles: fabrication and use for the treatment of brain glioma.

    PubMed

    Wu, Jia-Shuan; Mu, Li-Min; Bu, Ying-Zi; Liu, Lei; Yan, Yan; Hu, Ying-Jie; Bai, Jing; Zhang, Jing-Ying; Lu, Weiyue; Lu, Wan-Liang

    2017-03-29

    Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo. The results showed that the CNP-modified vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the brain glioma, and destroy neovasculatures effectively. The above mechanisms could be associated with the following aspects, namely, long circulation in the blood; drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated transcytosis; elimination of brain glioma cells and disruption of neovasculatures by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid vesicles could induce apoptosis of the glioma cells. The mechanisms could be related to the activations of caspase 8, caspase 3, p53, and reactive oxygen species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles could be used as a carrier material for treating brain glioma and disabling glioma neovasculatures.

  14. Cloning and sequence analysis of an Ophiophagus hannah cDNA encoding a precursor of two natriuretic peptide domains.

    PubMed

    Lei, Weiwei; Zhang, Yong; Yu, Guoyu; Jiang, Ping; He, Yingying; Lee, Wenhui; Zhang, Yun

    2011-04-01

    The king cobra (Ophiophagus hannah) is the largest venomous snake. Despite the components are mainly neurotoxins, the venom contains several proteins affecting blood system. Natriuretic peptide (NP), one of the important components of snake venoms, could cause local vasodilatation and a promoted capillary permeability facilitating a rapid diffusion of other toxins into the prey tissues. Due to the low abundance, it is hard to purify the snake venom NPs. The cDNA cloning of the NPs become a useful approach. In this study, a 957 bp natriuretic peptide-encoding cDNA clone was isolated from an O. hannah venom gland cDNA library. The open-reading frame of the cDNA encodes a 210-amino acid residues precursor protein named Oh-NP. Oh-NP has a typical signal peptide sequence of 26 amino acid residues. Surprisingly, Oh-NP has two typical NP domains which consist of the typical sequence of 17-residue loop of CFGXXDRIGC, so it is an unusual NP precursor. These two NP domains share high amino acid sequence identity. In addition, there are two homologous peptides of unknown function within the Oh-NP precursor. To our knowledge, Oh-NP is the first protein precursor containing two NP domains. It might belong to another subclass of snake venom NPs.

  15. The effect of discrete stimulation of carotid body chemoreceptors on atrial natriuretic peptide in anaesthetized dogs.

    PubMed Central

    al-Obaidi, M; Whitaker, E M; Karim, F

    1991-01-01

    1. In seven chloralose-anaesthetized and artificially ventilated beagles, the carotid sinus regions were vascularly isolated and perfused with either arterial or mixed (arterial and venous) blood (PO2 46.4 +/- 1.5 mmHg, mean +/- S.E.M.) to stimulate the chemoreceptors at constant flow and pressure. Cervical vagosympathetic trunks were ligated in all dogs, and gallamine triethiodide (2.0 mg kg-1 h-1, I.V.) was given in five dogs. Right atrial pressure was measured in all dogs, and left atrial pressure in four dogs. Mean aortic pressure was held constant (91.0 +/- 3.0 mmHg) by means of a reservoir connected to the animal via the common carotid and femoral arteries. Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay and urinary sodium by flame photometry. 2. In seven dogs with mean carotid sinus pressure maintained at 96.0 +/- 4.3 mmHg, stimulation of the carotid chemoreceptors for 25 min produced significant increases in left atrial pressure of 41.2 +/- 3.3% (n = 4; P less than 0.005) from 5.4 +/- 0.6 cmH2O and of 30.9 +/- 4.5% (n = 7; P less than 0.002) in ANP from 31.6 +/- 2.1 pg ml-1. However, chemoreceptor stimulation produced significant decreases in urine flow rate of 26.1 +/- 1.9% (n = 9; P less than 0.001) from 0.29 +/- 0.03 ml min-1 (100 g kidney weight)-1 and sodium excretion of 29.0 +/- 2.3% (P less than 0.001) from 8.5 +/- 1.7 mumol min-1 (100 g kidney weight)-1 but right atrial pressure and heart rate did not change significantly. In three of the dogs, beta-adrenoceptor blockade by atenolol (2 mg kg-1, I.V.) greatly reduced the effects of chemoreceptor stimulation on plasma levels of ANP. 3. The results show, for the first time, that discrete stimulation of the carotid chemoreceptors caused an increase in plasma ANP levels, probably due to the reflex increase in atrial pressure that results from an inhibition of the cardiac sympathetic nerves, and an increase in venous return from a reduction of peripheral vascular capacitance. PMID

  16. Atrial natriuretic peptide modulates the proliferation of human gastric cancer cells via KCNQ1 expression

    PubMed Central

    ZHANG, JIA; ZHAO, ZHILONG; ZU, CHAO; HU, HAIJIAN; SHEN, HUI; ZHANG, MINGXIN; WANG, JIANSHENG

    2013-01-01

    Atrial natriuretic peptide (ANP) and brain NP (BNP) belong to the NP family that regulates mammalian blood volume and blood pressure. ANP signaling through NP receptor A (NPR-A)/cyclic guanosine 3′5′-monophosphate (cGMP)/ cGMP-dependent protein kinase (PKG) activates various downstream effectors involved in cell growth, apoptosis, proliferation and inflammation. Evidence has shown the critical role of plasma K+ channels in the regulation of tumor cell proliferation. However, the role of ANP in the proliferation of gastric cancer cells is not clear. In the present study, the expression of NPR-A in the human gastric cancer cell line, AGS, and the effect of ANP on the proliferation of AGS cells were investigated using western blotting, immunofluorescence, qPCR and patch clamp assays. The K+ current was also analyzed in the effect of ANP on the proliferation of AGS cells. NPR-A was expressed in the human gastric cancer AGS cell line. Lower concentrations of ANP promoted the proliferation of the AGS cells, although higher concentrations decreased their proliferation. Significant increases in the levels of cGMP activity were observed in the AGS cells treated with 10−10, 10−9 and 10−8 M ANP compared with the controls, but no significant differences were observed in the 10−7 and 10−6 M ANP groups. The patch clamp results showed that 10−9 M ANP significantly increased the tetraethylammonium (TEA)- and 293B-sensitive K+ current, while 10−6 M ANP significantly decreased the TEA- and 293B-sensitive K+ current. The results showed that 10−10 and 10−9 M ANP significantly upregulated the expression of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) at the protein and mRNA levels, although 10−7 and 10−6 M ANP significantly downregulated the expression of KCNQ1. The data indicated that lower and higher concentrations of ANP have opposite effects on the proliferation of AGS cells through cGMP-dependent or -independent pathways. KCNQ1

  17. Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

    PubMed Central

    Menon, Bindu; Ramalingam, Krishnana; Conjeevaram, Jyoti; Munisusmitha, K.

    2016-01-01

    Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP) in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score on admission and functional disability by Barthel Index (BI) at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP). Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI) 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml) was very high as compared to controls (<60 ng/ml) (P < 0.001). There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00); NIHSS and BNP (R2 = 0.255; P < 0.01), negative correlation between BI and BNP (R2 = −0.064; P < 0.01). Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005). Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients. PMID:27994354

  18. Giant magnetic coercivity in YNi4B-type SmNi3TB (T=Mn-Cu) solid solutions

    NASA Astrophysics Data System (ADS)

    Yao, Jinlei; Yan, Chang; Yapaskurt, V. O.; Morozkin, A. V.

    2016-12-01

    The effects of transition metal substitution for Ni on the magnetic properties of the YNi4B-type SmNi4B via SmNi3TB (T=Mn, Fe, Co, Cu) solid solutions have been investigated. SmNi4B, SmNi3MnB, SmNi3FeB, SmNi3CoB and SmNi3CuB show ferromagnetic ordering at 40 K, 210 K, 322 K, 90 K and 57 K and field sensitive metamagnetic-like transitions at 15 K, 100 K, 185 K, 55 K and 15 K in a magnetic field of 10 kOe, respectively. The magnetocaloric effects of SmNi3TB (T=Mn-Cu) were calculated in terms of isothermal magnetic entropy change (ΔSm). The magnetic entropy ΔSm reaches value of -0.94 J/kg K at 40 K for SmNi4B, -1.5 J/kg K at 205 K for SmNi3MnB, -0.54 J/kg K at 320 K for SmNi3FeB, -0.49 J/kg K at 90 K for SmNi3CoB and -0.54 J/kg K at 60 K for SmNi3CuB in field change of 0-50 kOe around the Curie temperature. They show positive ΔSm of +0.71 J/kg K at ~10 K for SmNi4B, +1.69 J/kg K at 30 K for SmNi3MnB, +0.89 J/kg K at 110 K for SmNi3FeB, +1.08 J/kg K at 25 K for SmNi3CoB and +1.12 J/kg K at 10 K for SmNi3CuB in field change of 0-50 kOe around the low temperature metamagnetic-like transition. Below the field induced transition temperature (change of magnetic structure), SmNi3TB (T=Mn-Cu) exhibits giant magnetic coercivity of 74 kOe at 5 K for SmNi4B, 69 kOe at 20 K (90 kOe at 10 K) for SmNi3MnB, 77 kOe at 60 K for SmNi3FeB, 88 kOe at 20 K for SmNi3CoB and 52 kOe at 5 K for SmNi3CuB.

  19. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis

    PubMed Central

    Lou, Yiyun; Zhang, Fan; Luo, Yuqin; Wang, Liya; Huang, Shisi; Jin, Fan

    2016-01-01

    The ubiquitously expressed serum and glucocorticoid regulated kinase 1 (SGK1) is tightly regulated by osmotic and hormonal signals, including glucocorticoids and mineralocorticoids. Recently, SGK1 has been implicated as a signal hub for the regulation of sodium transport. SGK1 modulates the activities of multiple ion channels and carriers, such as epithelial sodium channel (ENaC), voltage-gated sodium channel (Nav1.5), sodium hydrogen exchangers 1 and 3 (NHE1 and NHE3), sodium-chloride symporter (NCC), and sodium-potassium-chloride cotransporter 2 (NKCC2); as well as the sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and type A natriuretic peptide receptor (NPR-A). Accordingly, SGK1 is implicated in the physiology and pathophysiology of Na+ homeostasis. Here, we focus particularly on recent findings of SGK1’s involvement in Na+ transport in renal sodium reabsorption, hormone-stimulated salt appetite and fluid balance and discuss the abnormal SGK1-mediated Na+ reabsorption in hypertension, heart disease, edema with diabetes, and embryo implantation failure. PMID:27517916

  20. [Serum sickness in diphtheria].

    PubMed

    Vozianova, Zh I; Chepilko, K I

    1999-01-01

    As many as 2247 patients with different clinical forms of diphtheria were examined. Antidiphtheric serum (ADS) was administered in 1556 children, the dosage being determined by condition of the patient. Serum sickness developed at day 7 to 9 in 24 (1.5%); 10 patients were found to run a mild course, 14--moderately severe. 6 patients had allergic reactions: 3--to antibiotic (penicillin), urticaria type, 1--to pertussoid-tetanic anatoxin, 2 had pollinosis-type reaction. Thus, serum sickness has practical value, which fact requires a detailed allergic history together with skin tests to be performed before the administration of ADS.

  1. Maternal serum screening.

    PubMed Central

    Carroll, J. C.

    1994-01-01

    Maternal serum screening (MSS) measures three serum markers: alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol, from which the risk of fetal Down syndrome or open neural tube defect is calculated. Initially, 8% of women will have positive results. I present a protocol for investigating these women. Family physicians should be informed about MSS so they can give their patients information and guidance. PMID:7524838

  2. Preparation of A-type proanthocyanidin dimers from peanut skins and persimmon pulp and comparison of the antioxidant activity of A-type and B-type dimers.

    PubMed

    Dong, Xiao-qian; Zou, Bo; Zhang, Ying; Ge, Zhen-zhen; Du, Jing; Li, Chun-mei

    2013-12-01

    We have established a simple method for preparing large quantities of A-type dimers from peanut skin and persimmon for further structure-activity relationship study. Peanut skins were defatted with hexane and oligomeric proanthocyanidins were extracted from it with 20% of methanol, and the extract was fractionated with ethyl acetate. Persimmon tannin was extracted from persimmon with methanol acidified with 1% hydrochloric acid, after removing the sugar and small phenols, the high molecular weight persimmon tannin was partially cleaved with 6.25% hydrochloric acid in methanol. The ethyl acetate fraction from peanut skins and persimmon tannin cleaved products was chromatographed on AB-8 macroporous resin followed by Toyopearl HW-50F resin to yield about 378.3mg of A-type (epi)catechin (EC) dimer from 1 kg dry peanut skins and 34.3mg of A-type (epi)catechin-3-O-gallate (ECG) dimer and 37.7 mg of A-type (epi)gallocatechin-3-O-gallate (EGCG) dimer from 1 kg fresh persimmon fruit. The antioxidant properties of the A-type and B-type dimers were compared in five different assays, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, hydroxyl radical, lipid peroxidation in mice liver homogenate and erythrocyte hemolysis in rat blood. Our results showed that both A-type and B-type dimers showed high antioxidant potency in a dose-dependent manner. In general, B-type dimers showed higher radical scavenging potency than A-type ones with the same subunits in aqueous systems. But in tissue or lipid systems, A-type dimers showed similar or even higher antioxidant potency than B-type ones.

  3. Constraining the Limits of the Magnetic Confinement-Rotation Diagram: An Analysis of Two B-type Systems Hosting Recently Discovered Extreme Centrifugal Magnetospheres

    NASA Astrophysics Data System (ADS)

    Sikora, James

    Following the detection in the late 70s of a strong magnetic field in the early B-type star sigma Ori E and, more recently with the results of the Magnetism In MassivE Stars (MiMeS) survey, an important and rare subclass of magnetic B-type stars has been emerging. Magnetic stars hosting so called "centrifugal magnetospheres" are characterized by rapid rotation and feature strong and broad emission lines in their spectra produced by a hot plasma co-rotating with the star well beyond the surface (at distances of several times the stellar radius). Since the first discovery of these properties in the magnetic B2Vp star sigma Ori E, the dense, rigidly-rotating circumstellar plasma has been understood as an accumulation of the star's wind in regions of closed magnetic loops above the surface. These objects serve as unique laboratories for studying how the fast winds emitted by all B-type stars interact with magnetic fields in extreme environments. In this study, the properties of two rapidly rotating stars, HD 23478 and HD 35502, hosts to centrifugal magnetospheres and exhibiting strong emission in their spectra, are derived. Our results establish new upper limits on the magnetic confinement-rotation diagram { a diagnostic tool which is used to understand the magnetospheres of O- and B-type stars in a broader context. The derived rapid rotation and strong magnetic fields imply that these two stars occupy the most extreme region of the magnetic confinement-rotation diagram populated by known centrifugal magnetosphere-hosting stars such as sigma Ori E and HR 5907.

  4. Role of atrial natriuretic peptide in mediating the blood pressure-independent natriuresis elicited by systemic inhibition of nitric oxide.

    PubMed

    Dobrowolski, Leszek; Kuczeriszka, Marta; Castillo, Alexander; Majid, Dewan S; Navar, L Gabriel

    2015-04-01

    While it is clearly recognized that increased intrarenal nitric oxide (NO) levels elicit natriuresis, confounding data showing that systemic nitric oxide synthase inhibition (NOSi) also increases sodium excretion (UNaV) poses a conundrum. This response has been attributed to the associated increases in arterial pressure (AP); however, the increases in AP and in UNaV are temporally dissociated. The changes in regional renal haemodynamics induced by NOSi could also contribute to the alterations of UNaV. To evaluate the roles of AP and non-AP mechanisms mediating the natriuresis, N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) was infused i.v. at doses ranging from 5 to 50 μg/kg/min in anaesthetized rats. UNaV, perfusion of the cortex (cortical blood flow, CBF) and medulla (medullary blood flow, MBF) with laser-Doppler flowmetry and glomerular filtration rate (GFR) were measured. UNaV increased from 0.6 ± 0.2 to 1.6 ± 0.1 μmol/kg/min (P < 0.05) with the lower nonpressor doses. With the higher doses, AP increased from 116 ± 4 to 122 ± 4 mmHg and UNaV increased from 1.1 ± 0.3 to 3.3 ± 0.7 μmol/min/g (P < 0.002). UNaV increased similarly in a group where renal AP was maintained at baseline levels. The associated reductions in CBF (17 ± 5 and 38 ± 5 %) and MBF (27 ± 6 and 52 ± 6 %) would be expected to attenuate rather than contribute to the natriuresis. Plasma atrial natriuretic peptide (ANP) concentrations increased significantly following NOSi. Anantin, a natriuretic peptide receptor-A blocker, prevented or reversed the L-NAME-induced natriuresis without altering the L-NAME-induced changes in AP or CBF. The results indicate that increased ANP and related natriuretic peptides mediate the AP-independent natriuresis, at least partly, elicited by systemic L-NAME infusion and help resolve the conundrum of natriuresis during systemic NOSi.

  5. The hybrid A/B type ν12 band of trans-ethylene-1,2-d2 by high-resolution Fourier transform infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Tan, T. L.; Ng, L. L.; Gabona, M. G.

    2015-06-01

    The FTIR absorption spectrum of the hybrid A/B type ν12 band of trans-ethylene-1,2-d2 (trans-C2H2D2) centered at 1298.038145(19) cm-1 in the 1220-1420 cm-1 region was recorded at an unapodized resolution of 0.0063 cm-1. Using Watson's A-reduced Hamiltonian in the Ir representation, a total of 2892 a- and b-type transitions was assigned and fitted to upper state (ν12 = 1) rovibrational constants up to three sextic terms. The b-type feature of the band was analyzed for the first time. The root-mean-square deviation of the upper state ν12 = 1 fit was 0.00037 cm-1 while the accuracy of the measurements of the line frequencies was limited to ±0.00065 cm-1. A set of ground state rovibrational constants up to three sextic terms was also derived from the simultaneous fit of 4597 ground state combination differences from the present analysis and those of the ν4 + ν8 and ν4 bands of trans-C2H2D2 with a root-mean-square deviation of 0.00039 cm-1. The transition dipole moment ratio |μa/μb | of the ν12 band of trans-C2H2D2 was found to be 5.0 ± 0.3.

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

    SciTech Connect

    Furukawa, Kazuhiro; Ishida, Kazuya; Tsunoyama, Taka-aki; Toda, Suguru; Osoda, Shinichi; Horigome, Tsuneyoshi; Fisher, Paul A.; Sugiyama, Shin

    2009-04-15

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

  7. Efficacy of vancomycin and teicoplanin alone and in combination with streptomycin in experimental, low-level vancomycin-resistant, VanB-type Enterococcus faecalis endocarditis.

    PubMed Central

    Nicolau, D P; Marangos, M N; Nightingale, C H; Patel, K B; Cooper, B W; Quintiliani, R; Courvalin, P; Quintiliani, R

    1996-01-01

    The efficacy of vancomycin (VM) and teicoplanin (TE), alone and in combination with streptomycin (SM), against enterococci that express low-level VanB-type VM resistance was investigated in experimental endocarditis using isogenic strains of Enterococcus faecalis susceptible to glycopeptides and aminoglycosides or inducibly resistant to low levels of VM (MIC = 16 micrograms/ml). VM was significantly less active against the resistant strain than against the susceptible strain, establishing that low-level VanB-type VM resistance can influence therapeutic efficacy. By contrast, TE had equally good activity against both strains. VM or TE combined with SM was synergistic and bactericidal against the resistant strain in vitro. While both combinations were efficient in reducing bacterial density in vivo, TE plus SM was significantly superior to VM plus SM if valve sterilization was considered. These data suggest that despite the presence of low-level VanB-type resistance, combination therapy with a glycopeptide and SM (and presumably other aminoglycosides to which there is not high-level resistance) will nevertheless provide effective bactericidal activity. PMID:8787879

  8. Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up-regulating natriuretic peptide receptor-A expression in the renal inner medullary collecting duct in decompensated heart failure.

    PubMed

    Liu, Chao; Chen, Ying; Kang, Yunxiao; Ni, Zhihua; Xiu, Heming; Guan, Jing; Liu, Kunshen

    2011-10-01

    In heart failure, the renal responsiveness to exogenous and endogenous atrial natriuretic peptide (ANP) is blunted. The mechanisms of renal hyporesponsiveness to ANP are complex, but one potential mechanism is decreased expression of natriuretic peptide receptor-A (NPR-A) in inner medullary collecting duct (IMCD) cells. Newly emerging evidence shows that glucocorticoids could produce potent diuresis and natriuresis in patients with heart failure, but the precise mechanism is unclear. In the present study, we found dexamethasone (Dex) dramatically increased the expression of NPR-A in IMCD cells in vitro. The NPR-A overexpression induced by Dex presented in a time- and dose-dependent manner, which emerged after 12 h and peaked after 48 h. The cultured IMCD cells were then stimulated with exogenous rat ANP. Consistent with the findings with NPR-A expression, Dex greatly increased cGMP (the second messenger for the ANP) generation in IMCD cells, which presented in a time- and dose-dependent manner as well. In rats with decompensated heart failure, Dex dramatically increased NPR-A expression in inner renal medulla, which was accompanied by a remarkable increase in renal cGMP generation, urine flow rate, and renal sodium excretion. It is noteworthy that Dex dramatically lowered plasma ANP, cGMP levels, and left ventricular end diastolic pressure. These favorable effects induced by Dex were glucocorticoid receptor (GR)-mediated and abolished by the GR antagonist 17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one (RU486). Collectively, glucocorticoids could improve renal responsiveness to ANP by up-regulating NPR-A expression in the IMCD and induce a potent diuretic action in rats with decompensated heart failure.

  9. Distribution of C-type natriuretic peptide and its messenger RNA in rat central nervous system and peripheral tissue.

    PubMed

    Minamino, N; Aburaya, M; Kojima, M; Miyamoto, K; Kangawa, K; Matsuo, H

    1993-11-30

    In rat, the highest concentration of immunoreactive (ir-) C-type natriuretic peptide (CNP) was found in the central nervous system, as is the case in pig and human. Although its concentration in peripheral tissue was much lower than that in brain, CNP was present mainly as CNP-53 in ileum-jejunum, colon-cecum, stomach, kidney, lung, testis and submaxillary gland, but not in heart. By Northern blot analysis, CNP mRNA was detected in ileum-jejunum, testis, thymus, adrenal gland and submaxillary gland as well as in brain and spinal cord. CNP mRNA was further verified by reverse transcription-polymerase chain reaction to be present in most peripheral tissue, including aorta and bone marrow. These results indicate that CNP is synthesized in peripheral tissue and possibly functions as a local regulator in addition to acting as a neuropeptide in the central nervous system.

  10. Increased atrial natriuretic peptide (6-33) binding sites in the subfornical organ of water deprived and Brattleboro rats

    SciTech Connect

    Saavedra, J.M.; Israel, A.; Correa, F.M.A.; Kurihara, M.

    1986-09-01

    Binding sites for rat atrial natriuretic eptide (6-33) (ANP) were quantitated in the subfornical organ of chronically dehydrated homozygous Brattleboro rats unable to synthesize vasopressin; heterozygous Brattleboro rats, their controls, Long Evans rats and Long Evans rats after 4 days of water deprivation. Brain sections were incubated in the presence of /sup 125/I-ANP and the results analyzed by autoradiography coupled to computerized microdensitometry and comparison to /sup 125/I-standards. Brattleboro rats and water deprived Long Evans rats presented a higher number of ANP binding sites than their normally hydrated controls. The results suggest a role of ANP binding sites in the subfornical organ in the central regulation of fluid balance and vasopressin secretion.

  11. Decreased atrial natriuretic factor receptors and impaired cGMP generation in glomeruli from the cardiomyopathic hamster.

    PubMed

    Levin, E R; Frank, H J; Chaudhari, A; Kirschenbaum, M A; Bandt, A; Mills, S

    1989-03-15

    To determine a possible basis for the decreased action of atrial natriuretic factors (ANF) in congestive heart failure, we compared the cardiomyopathic hamster (CMH) in frank congestive failure, and the age-matched, normal, F1B strain of Golden Syrian Hamsters. Scatchard analysis of competitive binding studies revealed two classes of glomerular receptors. The CMH exhibited decreased binding overall and a markedly decreased number of high affinity receptors but comparable receptor affinity compared to the F1B. In contrast, the low affinity receptor population in the CMH had a much greater affinity compared to the F1B while receptor number was similar. Plasma ANF levels were substantially elevated in the CMH compared to the F1B and in-vitro generation of cGMP was significantly lower in the CMH. Such abnormalities could contribute to the resistance to ANF in this disease.

  12. Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease.

    PubMed

    Kitagawa, H; Kitoh, K; Inoue, H; Ohba, Y; Suzuki, F; Sasaki, Y

    2000-04-01

    Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

  13. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  14. Effects of atrial and brain natriuretic peptides upon cyclic GMP levels, potassium transport, and receptor binding in rat astrocytes

    SciTech Connect

    Beaumont, K.; Tan, P.K. )

    1990-02-01

    The ability of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) to alter cyclic GMP levels and NaKCl cotransport in rat neocortical astrocytes was determined. At concentrations of 10(-9)-10(-6) M, rat ANP99-126 (rANF), rat ANP102-126 (auriculin B), and rat ANP103-126 (atriopeptin III) stimulated 6- to 100-fold increases in cyclic GMP levels. Porcine BNP (pBNP) and rat BNP (rBNP) were 20%-90% as effective as rANF over most of this concentration range, although 10(-6) M pBNP produced a greater effect than rANF. NaKCl cotransport as measured by bumetanide-sensitive 86Rb+ influx was not altered by exposure of astrocytes to 10(-6)M rANF, pBNP, or rBNP. Both pBNP and rBNP, as well as rat ANP103-123 (atriopeptin I) and des(gl18, ser19, gly20, leu21, gly22) ANF4-23-NH2 (C-ANF4-23) strongly competed for specific 125I-rANF binding sites in astrocyte membranes with affinities ranging from 0.03 to 0.4 nM, suggesting that virtually all binding sites measured at subnanomolar concentrations of 125I-rANF were of the ANP-C (ANF-R2) receptor subtype. These receptors are thought to serve a clearance function and may be linked to a guanylate cyclase activity that is chemically and pharmacologically distinct from that coupled to ANP-A (ANF-R1) receptors. ANP receptors on astrocytes may function in limiting the access of ANP and BNP to neurons involved in body fluid and cardiovascular regulation.

  15. Muscarinic activity modulated by C-type natriuretic peptide in gastric smooth muscles of guinea-pig stomach.

    PubMed

    Xing, De-gang; Huang, Xu; Li, Chun-hui; Li, Xiang-lan; Piao, Lian-hua; Gao, Ling; Zhang, Yang; Kim, Yong-chul; Xu, Wen-xie

    2007-10-04

    Natriuretic peptides (NPs) are a cyclic guanosine monophosphate (cGMP) generation system like nitric oxide (NO) and play an inhibitory regulation in gastrointestinal motility but the effect of NPs on muscarinic activity is still unclear. This study was designed to investigate effect of C-type natriuretic peptide (CNP) on muscarinic control of gastric motility and its ion channel mechanism. The spontaneous contraction of gastric smooth muscle strip was recorded by using physiograph in guinea-pig. Membrane currents and potential were recorded by using whole-cell patch-clamp technique. CNP significantly inhibited muscarinic M receptor agonist carbachol (Cch)-induced contractions of gastric smooth muscle strips and dramatically hyperpolarized Cch-induced depolarization of membrane potential in gastric single smooth muscle cell. Muscarinic currents induced by both Cch and GTPgammaS, a G-protein agonist were significantly suppressed by CNP. 8-Br-cGMP mimicked the effect of CNP on Cch-induced muscarinic currents, and the peak holding current was decreased from -200.66+/-54.35 pA of control to -67.35+/-24.82 pA. LY83583, a guanylate cyclase nonspecific inhibitor, significantly weakened the inhibitory effect of CNP on muscarinic current while zaprinast, a cGMP sensitive phosphoesterase inhibitor, potentiated the inhibitory effect of CNP on muscarinic current. cGMP production was dramatically enhanced by CNP and this effect was suppressed by LY83583 in gastric smooth muscle. These results suggest that CNP modulates muscarinic activity via CNP-NPR-particulate guanylate cyclase (pGC)-cGMP pathway in guinea-pig.

  16. Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

    PubMed

    Wang, Dong; Gladysheva, Inna P; Fan, Tai-Hwang M; Sullivan, Ryan; Houng, Aiilyan K; Reed, Guy L

    2014-03-01

    Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

  17. Localization of atrial natriuretic peptide mRNA and immunoreactivity in the rat heart and human atrial appendage

    SciTech Connect

    Hamid, Q.; Wharton, J.; Terenghi, G.; Hassall, C.J.S.; Aimi, J.; Taylor, K.M.; Nakazato, H.; Dixon, J.E.; Burnstock, G.; Polak, J.M.

    1987-10-01

    The localization of mRNA encoding preproatrial natriuretic peptide was investigated in tissue sections and cultures of rat heart and in sections of human right atrial appendage using the technique of in situ hybridization with /sup 32/P- and /sup 35/S-labeled RNA probes. Rat atrial natriuretic peptide (ANP) transcripts were demonstrated in numerous atrial myocytes and, to a lesser extent, in ventricular myocytes in both tissue sections and newborn rat heart cultures. These findings are consistent with those obtained by RNA blot analysis of rat heart total RNA, indicating that a single prepro-ANP transcript of approx. 900 nucleotides was present in the ventricles as well as the atria. Using a /sup 35/S-labeled RNA probe for human ANP mRNA, ANP transcripts were also localized to the majority of myocytes in the human right atrial appendage. Only background levels of autoradiographic labeling were obtained when RNA probes identical to the coding sequence of rat or human ANP mRNA were used. A close correlation was found between the distribution of ANP immunoreactivity and prepro-ANP mRNA in these preparations. These results provide unequivocal evidence for the expression of the ANP gene in the rat ventricles, as well as the atria, because myocytes in these tissues have been established as the sites of both ANP localization and precursor biosynthesis. The combined use of cardiac cultures and in situ hybridization may be of value in future studies investigating the regulation of ANP synthesis in cardiac myocytes.

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

    PubMed Central

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

    2016-01-01

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

  19. [Indications and Clinical Implications of the Use of the Cardiac Markers BNP and NT-proBNP].

    PubMed

    Luchner, Andreas; von Haehling, Stephan; Holubarsch, Christian; Keller, Till; Knebel, Fabian; Zugck, Christian; Laufs, Ulrich

    2017-03-01

    B-type natriuretic peptides are markers of myocardial wall stress. BNP or NT-proBNP are used for the differential diagnosis of acute dyspnoe where normal serum concentrations make a cardiac cause unlikely. New data show their importance for risk prediction in different stages of heart failure and in primary prevention. Natriuretic peptide guided therapy improves titration of heart failure medications. Compared to BNP, NT-proBNP is better suited during therapy with the new angiotensin-rezeptor-neprilysin-inhibitor Sacubitril/Valsartan. This review article summarizes current data on the importance of B-type natriuretic peptides for the interface of ambulatory and hospital care and presents recommendations for their practical use in patient care.

  20. Serum albumins - unusual allergens

    PubMed Central

    Chruszcz, Maksymilian; Mikolajczak, Katarzyna; Mank, Nicholas; Majorek, Karolina A.; Porebski, Przemyslaw J.; Minor, Wladek

    2015-01-01

    Background Albumins are multifunctional proteins present in the blood serum of animals. They can bind and transport a wide variety of ligands which they accommodate due to their conformational flexibility. Serum albumins are highly conserved both in amino acid sequence and three-dimensional structure. Several mammalian and avian serum albumins (SAs) are also allergens. Sensitization to one of the SAs coupled with the high degree of conservation between SAs may result in cross-reactive antibodies in allergic individuals. Sensitivity to SA generally begins with exposure to an aeroallergen, which can then lead to cross-sensitization to serum albumins present in food. Scope of Review This review focuses on the allergenicity of SAs presented in a structural context. Major Conclusions SA allergenicity is unusual taking into account the high sequence identity and similarity between SA from different species and human serum albumin. Cross-reactivity of human antibodies towards different SAs is one of the most important characteristics of these allergens. General Significance Establishing a relationship between sequence and structure of different SAs and their interactions with antibodies is crucial for understanding the mechanisms of cross-sensitization of atopic individuals. Structural information can also lead to better design and production of recombinant SAs to replace natural proteins in allergy testing and desensitization. Therefore, structural analyses are important for diagnostic and treatment purposes. PMID:23811341

  1. A double helix B-type geometry based on high-resolution proton NMR of single-helical DNA fragments: d(TA)5 x d(TA)5.

    PubMed Central

    Mellema, J R; van Kampen, P N; Carlson, C N; Bosshard, H E; Altona, C

    1983-01-01

    A single-helical B-type geometry is presented based on 1H NMR observations on d(TATA) and several other small single-helical DNA fragments. The structure is extended to one complete turn of double-helical DNA and its characteristics are compared with other known B-type structures. PMID:6856480

  2. SERUM SICKNESS IN RABBITS

    PubMed Central

    Fleisher, Mover S.; Jones, Lloyd

    1931-01-01

    1. The injection of a single large dose of normal horse serum into rabbits results in the appearance 3 to 8 days later of erythematous and edematous reactions on the ears in 68.9 per cent of the animals. 2. The injections may be given by any of several routes and reactions appear when the site of injection is definitely distant from the ears. 3. Injections of various antisera into rabbits cause the appearance of similar reactions. 4. These reactions can be considered as manifestations of serum sickness in rabbits. PMID:19869943

  3. Canine Recombinant Adenovirus Vector Induces an Immunogenicity-Related Gene Expression Profile in Skin-Migrated CD11b+ -Type DCs

    PubMed Central

    Jouneau, Luc; Bourge, Mickael; Bouet-Cararo, Coraline; Bonneau, Michel; Zientara, Stephan; Klonjkowski, Bernard; Schwartz-Cornil, Isabelle

    2012-01-01

    Gene expression profiling of the blood cell response induced early after vaccination has previously been demonstrated to predict the immunogenicity of vaccines. In this study, we evaluated whether the analysis of the gene expression profile of skin-migrated dendritic cells (DCs) could be informative for the in vitro prediction of immunogenicity of vaccine, using canine adenovirus serotype 2 (CAV2) as vaccine vector. CAV2 has been shown to induce immunity to transgenes in several species including sheep and is an interesting alternative to human adenovirus-based vectors, based on the safety records of the parental strain in dogs and the lack of pre-existing immunity in non-host species. Skin-migrated DCs were collected from pseudo-afferent lymph in sheep. Both the CD11b+ -type and CD103+ -type skin-migrated DCs were transduced by CAV2. An analysis of the global gene response to CAV2 in the two skin DC subsets showed that the gene response in CD11b+ -type DCs was far higher and broader than in the CD103+ -type DCs. A newly released integrative analytic tool from Ingenuity systems revealed that the CAV2-modulated genes in the CD11b+ -type DCs clustered in several activated immunogenicity-related functions, such as immune response, immune cell trafficking and inflammation. Thus gene profiling in skin-migrated DC in vitro indicates that the CD11b+ DC type is more responsive to CAV2 than the CD103+ DC type, and provides valuable information to help in evaluating and possibly improving viral vector vaccine effectiveness. PMID:23300693

  4. Comparisons of CVID and IgGSD: referring physicians, autoimmune conditions, pneumovax reactivity, immunoglobulin levels, blood lymphocyte subsets, and HLA-A and -B typing in 432 adult index patients.

    PubMed

    Barton, James C; Bertoli, Luigi F; Barton, J Clayborn

    2014-01-01

    Common variable immunodeficiency (CVID) and immunoglobulin (Ig) G subclass deficiency (IgGSD) are heterogeneous disorders characterized by respiratory tract infections, selective Ig isotype deficiencies, and impaired antibody responses to polysaccharide antigens. Using univariable analyses, we compared observations in 34 CVID and 398 IgGSD adult index patients (81.9% women) referred to a hematology/oncology practice. Similarities included specialties of referring physicians, mean ages, proportions of women, reactivity to Pneumovax, median serum IgG3 and IgG4 levels, median blood CD56+/CD16+ lymphocyte levels, positivity for HLA-A and -B types, and frequencies of selected HLA-A, -B haplotypes. Dissimilarities included greater prevalence of autoimmune conditions, lower median IgG, IgA, and IgM, and lower median CD19+, CD3+/CD4+, and CD3+/CD8+ blood lymphocytes in CVID patients. Prevalence of Sjögren's syndrome and hypothyroidism was significantly greater in CVID patients. Combined subnormal IgG1/IgG3 occurred in 59% and 29% of CVID and IgGSD patients, respectively. Isolated subnormal IgG3 occurred in 121 IgGSD patients (88% women). Logistic regression on CVID (versus IgGSD) revealed a significant positive association with autoimmune conditions and significant negative associations with IgG1, IgG3, and IgA and CD56+/CD16+ lymphocyte levels, but the odds ratio was increased for autoimmune conditions alone (6.9 (95% CI 1.3, 35.5)).

  5. Serum Bilirubin and 6-min Walk Distance as Prognostic Predictors for Inoperable Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study

    PubMed Central

    Gong, Juan-Ni; Zhai, Zhen-Guo; Yang, Yuan-Hua; Liu, Yan; Gu, Song; Kuang, Tu-Guang; Xie, Wan-Mu; Miao, Ran; Wang, Chen

    2015-01-01

    Background: Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is a severe clinical syndrome characterized by right cardiac failure and possibly subsequent liver dysfunction. However, whether serum markers of liver dysfunction can predict prognosis in inoperable CTEPH patients has not been determined. Our study aimed to evaluate the potential role of liver function markers (such as serum levels of transaminase, bilirubin, and gamma-glutamyl transpeptidase [GGT]) combined with 6-min walk test in the prediction of prognosis in patients with inoperable CTEPH. Methods: From June 2005 to May 2013, 77 consecutive patients with inoperable CTEPH without confounding co-morbidities were recruited for this prospective cohort study. Baseline clinical characteristics and 6-min walk distance (6MWD) results were collected. Serum biomarkers of liver function, including levels of aspartate aminotransferase, alanine aminotransferase, GGT, uric acid, and serum bilirubin, were also determined at enrollment. All-cause mortality was recorded during the follow-up period. Results: During the follow-up, 22 patients (29%) died. Cox regression analyses demonstrated that increased serum concentration of total bilirubin (hazard ratio [HR] = 7.755, P < 0.001), elevated N-terminal of the prohormone brain natriuretic peptide (HR = 1.001, P = 0.001), decreased 6MWD (HR = 0.990, P < 0.001), increased central venous pressure (HR = 1.074, P = 0.040), and higher pulmonary vascular resistance (HR = 1.001, P = 0.018) were associated with an increased risk of mortality. Serum concentrations of total bilirubin (HR = 4.755, P = 0.007) and 6MWD (HR = 0.994, P = 0.017) were independent prognostic predictors for CTEPH patients. Patients with hyperbilirubinemia (≥23.7 μmol/L) had markedly worse survival than those with normobilirubinemia. Conclusion: Elevated serum bilirubin and decreased 6MWD are potential predictors for poor prognosis in inoperable CTEPH. PMID:26612283

  6. B-type cyclins regulate G1 progression in fission yeast in opposition to the p25rum1 cdk inhibitor.

    PubMed Central

    Martin-Castellanos, C; Labib, K; Moreno, S

    1996-01-01

    The onset of S phase in fission yeast is regulated at Start, the point of commitment to the mitotic cell cycle. The p34cdc2 kinase is essential for G1 progression past Start, but until now its regulation has been poorly understood. Here we show that the cig2/cyc17 B-type cyclin has an important role in G1 progression, and demonstrate that p34cdc2 kinase activity is periodically associated with cig2 in G1. Cells lacking cig2 are defective in G1 progression, and this is particularly clear in small cells that must regulate Start with respect to cell size. We also find that the cig1 B-type cyclin can promote G1 progression. Whilst p25rum1 can inhibit cig2/cdc2 activity in vitro, and may transiently inhibit this complex in vivo, cig1 is regulated independently of p25rum1. Since cig1/cdc2 kinase activity peaks in mitotic cells, and decreases after mitosis with similar kinetics to cdc13-associated kinase activity, we suggest that cig2 is likely to be the principal fission yeast G1 cyclin. cig2 protein levels accumulate in G1 cells, and we propose that p25rum1 may transiently inhibit cig2-associated p34cdc2 activity until the critical cell size required for Start is reached. Images PMID:8631305

  7. Heat resistant reduced activation 12% Cr steel of 16Cr12W2VTaB type-advanced structural material for fusion and fast breeder power reactors

    NASA Astrophysics Data System (ADS)

    Ioltukhovskiy, A. G.; Leonteva-Smirnova, M. V.; Solonin, M. I.; Chernov, V. M.; Golovanov, V. N.; Shamardin, V. K.; Bulanova, T. M.; Povstyanko, A. V.; Fedoseev, A. E.

    2002-12-01

    Heat resistant 12% Cr steels of the 16Cr12W2VTaB type (12Cr-2W-V-Ta-B-0.16C) provide a reduced activation material that can be used as a structural material for fusion and fast breeder reactors. The composition under study meets scientific and engineering requirements and has an optimal base element composition to provide a δ-ferrite content of no more than 20%. It also has a minimum quantity of low melting impurity elements and non-metallic inclusions. Short-term tensile properties for the steel tested to 700 °C are provided after the standard heat treatment (normalization, temper). Rupture strength and creep properties for the steel depending on the initial heat treatment conditions are also given. The microstructural stability of the 16Cr12W2VTaB type steel at temperatures up to 650 °C is predicted to be good, and the properties of the steel after irradiation in BOR-60 are demonstrated.

  8. Importance of hydrophobic interaction between a SoxB-type cytochrome c oxidase with its natural substrate cytochrome c-551 and its mutants.

    PubMed

    Kagekawa, Sayaka; Mizukami, Makoto; Noguchi, Shunsuke; Sakamoto, Junshi; Sone, Nobuhito

    2002-08-01

    Cytochrome c-551, the electron donor of SoxB-type cytochrome c oxidase in thermophilic bacilli, can be over-expressed in Bacillus thermodenitrificans cells by tranformation with pSTEc551. Several mutant cytochromes c-551 were prepared by site-directed mutagenesis to this expression plasmid. Among them, several Lys residues were changed to Ala/Ser, and we found that these mutant cytochromes retained their activity as substrates, although their K(m) values were 0.04-0.12 microM, depending on the site replaced. In contrast, the C19A mutant cytochrome, which was produced in Brevibacillus choshinensis as a secretion protein, lost its activity as a substrate, suggesting that the fatty acyl-glyceryl residue covalently bound to the cysteine residue of the wild-type c-551 plays a very important role in the activity. The importance of the hydrophobic fatty acid residue for the binding of cytochrome c-551 to the oxidase was also shown by the loss of substrate activity in deacylated cytochrome c-551. These results show the importance of the hydrophobic interaction between this cytochrome and SoxB-type oxidase, despite the fact that the importance of an electrostatic interaction between cytochrome c and mitochondrial cytochrome aa(3) oxidase has already been established.

  9. B-type nuclear lamin and the nuclear pore complex Nup107-160 influences maintenance of the spindle envelope required for cytokinesis in Drosophila male meiosis

    PubMed Central

    Hayashi, Daisuke; Tanabe, Karin; Katsube, Hiroka

    2016-01-01

    ABSTRACT In higher eukaryotes, nuclear envelope (NE) disassembly allows chromatin to condense and spindle microtubules to access kinetochores. The nuclear lamina, which strengthens the NE, is composed of a polymer meshwork made of A- and B-type lamins. We found that the B-type lamin (Lam) is not fully disassembled and continues to localize along the spindle envelope structure during Drosophila male meiosis I, while the A-type lamin (LamC) is completely dispersed throughout the cytoplasm. Among the nuclear pore complex proteins, Nup107 co-localized with Lam during this meiotic division. Surprisingly, Lam depletion resulted in a higher frequency of cytokinesis failure in male meiosis. We also observed the similar meiotic phenotype in Nup107-depleted cells. Abnormal localization of Lam was found in the Nup-depleted cells at premeiotic and meiotic stages. The central spindle microtubules became abnormal and recruitment of a contractile ring component to the cleavage sites was disrupted in Lam-depleted cells and Nup107-depleted cells. Therefore, we speculate that both proteins are required for a reinforcement of the spindle envelope, which supports the formation of central spindle microtubules essential for cytokinesis in Drosophila male meiosis. PMID:27402967

  10. Studies of peptide a- and b-type fragment ions using stable isotope labeling and integrated ion mobility/tandem mass spectrometry.

    PubMed

    Riba Garcia, Isabel; Giles, Kevin; Bateman, Robert H; Gaskell, Simon J

    2008-12-01

    The structures of peptide a- and b-type fragment ions were studied using synthetic peptides including a set of isomeric peptides, differing in the sequence location of an alanine residue labeled with (15)N and uniformly with (13)C. The pattern of isotope labeling of second-generation fragment ions derived via a(n) and b(n) ions (where n = 4 or 5) suggested that these intermediates existed in part as macrocyclic structures, where alternative sites of ring opening gave rise to different linear forms whose simple cleavage might give rise to the observed final products. Similar conclusions were derived from combined ion mobility/tandem MS analyses where different fragmentation patterns were observed for isomeric a- or b-type ions that display different ion mobilities. These analyses were facilitated by a new approach to the processing of ion mobility/tandem MS data, from which distinct and separate product ion spectra are derived from ions that are incompletely separated by ion mobility. Finally, an example is provided of evidence for a macrocyclic structure for b(n) ions where n = 8 or 9.

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

    PubMed Central

    Ding, Zhili; Luo, Na; Kong, Youqin; Li, Jingfen; Zhang, Yixiang; Cao, Fang

    2016-01-01

    The scavenger receptor class B, type I (SR-BI), is a member of the CD36 superfamily comprising transmembrane proteins involved in mammalian and fish lipid homeostasis regulation. We hypothesize that this receptor plays an important role in Macrobrachium nipponense lipid metabolism. However, little attention has been paid to SR-BI in commercial crustaceans. In the present study, we report a cDNA encoding M. nipponense scavenger receptor class B, type I (designated as MnSR-BI), obtained from a hepatopancreas cDNA library. The complete MnSR-BI coding sequence was 1545 bp, encoding 514 amino acid peptides. The MnSR-BI primary structure consisted of a CD36 domain that contained two transmembrane regions at the N- and C-terminals of the protein. SR-BI mRNA expression was specifically detected in muscle, gill, ovum, intestine, hepatopancreas, stomach, and ovary tissues. Furthermore, its expression in the hepatopancreas was regulated by dietary lipid sources, with prawns fed soybean and linseed oils exhibiting higher expression levels. RNAi-based SR-BI silencing resulted in the suppression of its expression in the hepatopancreas and variation in the expression of lipid metabolism-related genes. This is the first report of SR-BI in freshwater prawns and provides the basis for further studies on SR-BI in crustaceans. PMID:28003996

  12. Assays of Serum Testosterone.

    PubMed

    Herati, Amin S; Cengiz, Cenk; Lamb, Dolores J

    2016-05-01

    The diagnosis of male hypogonadism depends on an assessment of the clinical signs and symptoms of hypogonadism and serum testosterone level. Current clinical laboratory testosterone assay platforms include immunoassays and mass spectrometry. Despite significant advances to improve the accuracy and precision of the currently available assays, limited comparability exists between assays at the lower and upper extremes of the testosterone range. Because of this lack of comparability, there is no current gold standard assay for the assessment of total testosterone levels.

  13. The Human Serum Metabolome

    PubMed Central

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  14. Use of serum ultrafiltrate in the serum dilution test.

    PubMed

    Leggett, J E; Wolz, S A; Craig, W A

    1989-10-01

    Although pooled human serum diluent is advocated in the serum dilution test, its use may compensate for protein binding defects in patients and yield nonrepresentative titers. To test this hypothesis, comparison was made of serum ultrafiltrate (molecular weight cutoff less than or equal to 30,000) serially diluted into either pooled serum ultrafiltrate or Mueller-Hinton broth with patient serum samples diluted into pooled human serum in 111 assays from 55 patients and 6 volunteers. Of 111 bactericidal titers in ultrafiltrate and/or Mueller-Hinton broth, 101 were within a single twofold dilution of titers in pooled human serum. Nine of 10 discordant titers involved highly bound drugs and were usually higher in ultrafiltrate than in pooled human serum. In seven additional volunteers with renal failure, titers in ultrafiltrate and in each volunteer's serum were higher than those diluted in pooled human serum (P = .002). Recommended methods using pooled serum diluent may not accurately predict actual bactericidal titers in patients with abnormal protein binding.

  15. Relationship between serum sodium level and coronary artery abnormality in Kawasaki disease

    PubMed Central

    Park, Sora; Kim, Ji Hong

    2017-01-01

    Purpose Kawasaki disease (KD) is an immune-related multisystemic vasculitis that occurs in children, especially ensuing from a coronary artery abnormality. Sodium level is known to be related to vascular injury, which could affect the progress of KD. The purpose of this study was to determine the serum sodium levels that could predict the occurrence of cardiac and coronary artery events in KD. Methods We conducted a retrospective review of medical records for 104 patients with KD from January 2015 to December 2015. Patients with serum Na levels of <135 mEq/L at the time of initial diagnosis were assigned to the hyponatremia group. Laboratory findings and echocardiographic data were analyzed for various aspects. Results Among the 104 patients with KD, 91 were included in the study, of whom 48 (52.7%) had hyponatremia. The degree of fever, white blood cell count, percentage of neutrophils, percentage of lymphocytes, total bilirubin level, brain natriuretic peptide level, erythrocyte sedimentation rate, and C-reactive protein level were higher in the patients with hyponatremia. They also demonstrated a trend of larger coronary artery diameters based on Z scores. Conclusion The severity of vascular inflammation in acute KD with hyponatremia might worsen the prognosis of coronary vasculature. Although no statistically significant correlation was found between the initial serum sodium levels and coronary arteriopathy in the patients with KD in this study, a long-term follow-up study with a larger number of enrolled patients should be designed in the future to elucidate the relationship between serum sodium level and coronary arteriopathy in patients with KD. PMID:28289432

  16. Brain natriuretic peptide as a biomarker of asymptomatic clozapine-related heart dysfunction: a criterion for a more cautious administration.

    PubMed

    Prisco, Vincenzo; Monica, Petrosino; Fiore, Germano; Tridente, Annamaria; La Rocca, Antonietta; Catapano, Francesco; Fabrazzo, Michele

    2016-12-20

    Clozapine-related pericarditis is a rare side effect of the drug. We reported the clinical cases of two women, aged 22 and 28 years, affected by schizophrenia with pericarditis symptoms related to clozapine treatment of 200 mg/day. Clozapine was discontinued in both patients, resulting in normalization of the ECG changes, and echocardiography confirmed the progressive disappearance of the pericardial effusion. Interestingly, while inflammatory indices and pro-brain natriuretic peptide (pro-BNP) plasma levels were high in both patients, only one of them showed tachycardia, subjective chest pain, shortness of breath and dyspnea, with a clinical symptomatology suggesting a cardiac involvement. BNP is a vasoactive peptide synthetized by the ventricular myocardium which splits in two fragments: BNP and the N-terminal (pro-BNP). Both are considered valuable biomarkers in clinical practice for the prediction of disease state and prognosis in patients with suspected heart failure. Pro-BNP acts as a key regulator in the homeostasis of water and salt excretion and in the maintenance of blood pressure, mainly by inhibiting the renin-angiotensin-aldosterone axis and blocking the sympathetic nervous activity. In our cases, pro-BNP plasma levels proved to be a profitable way to identify subjects with asymptomatic cardiac impairment who could benefit from a therapy preventing progression to heart failure.

  17. N-terminal-pro-brain natriuretic peptide is decreased in insulin dependent gestational diabetes mellitus: a prospective cohort trial

    PubMed Central

    2011-01-01

    Background N-terminal-pro-brain natriuretic peptide (NT-proBNP) is elevated in gestational hypertension and preeclampsia. This trial aimed to generate data for gestational diabetes mellitus patients, who are at risk to develop these complications. Methods We have measured NT-proBNP in 223 otherwise healthy women between gestational week 24 and 32 referred to the outpatient diabetes unit in a cross-sectional study. Results 88 control subjects, 45 patients with indication for medical nutrition therapy (MNT) alone and 90 patients who required insulin therapy were included. Groups of women were comparable regarding gestational week. Body mass index before pregnancy and at blood draw was significantly higher in subjects with insulin dependent gestational diabetes mellitus compared to MNT controlled gestational diabetes mellitus. NT-proBNP was significantly lower in patients with insulin dependent gestational diabetes mellitus (35 ± 25 pg/ml) compared to controls (53 ± 43 pg/ml, p = 0.012). Conclusions NT-proBNP is within the reference range of normal subjects in women with gestational diabetes mellitus. Differences in body mass index, changes in glomerular filtration rate and haemodynamics may explain lower NT-proBNP concentrations in insulin dependent gestational diabetes mellitus. A false negative interpretation needs to be considered in these women. PMID:21489265

  18. Characterization and purification of the detergent solubilized atrial natriuretic peptide receptor from bovine aortic smooth muscle cells

    SciTech Connect

    Schenk, D.; Phelps, M.; Scarborough, R.; Johnson, K.; Lewicki, J.

    1986-03-01

    A protein has been purified from total homogenates of cultured vascular bovine smooth muscle cells with properties indicative of the receptor for atrial natriuretic peptide (ANP). Specific /sup 125/I-ANP binding activity was solubilized quantitatively from smooth muscle cell membranes with a purified component of Triton X-100. Equilibrium binding studies of the solubilized ANP receptor reveal by Scatchard analysis a single class of binding sites with a K/sub d/ = 1.77 x 10/sup -10/ moles /sup 125/I-ANP/1 and B/sub max/ = 34.6 pmol/mg protein. The ANP receptor solubilized in this manner is stable for greater than or equal to 2 months at -70/sup 0/C. Studies investigating the ANP receptor show that it binds to wheat germ agglutinin and to CM-cellulose at pH 4.1 but not at pH 6.5. These findings imply that the ANP receptor is a neutral to mildly basic glycoprotein. Further purification studies involving affinity chromatography with ANP-Sepharose result in a 500-fold purification and reveal a single protein with a molecular mass of 58,700 daltons as determined by SDS-polyacrylamide gel electrophoresis. The size of this protein is in good agreement with that of an ANP receptor previously identified in intact smooth muscle cells by crosslinking studies with /sup 125/I-ANP.

  19. Pharmacological Therapy in the Heart as an Alternative to Cellular Therapy: A Place for the Brain Natriuretic Peptide?

    PubMed Central

    Rosenblatt-Velin, Nathalie; Badoux, Suzanne; Liaudet, Lucas

    2016-01-01

    The discovery that stem cells isolated from different organs have the ability to differentiate into mature beating cardiomyocytes has fostered considerable interest in developing cellular regenerative therapies to treat cardiac diseases associated with the loss of viable myocardium. Clinical studies evaluating the potential of stem cells (from heart, blood, bone marrow, skeletal muscle, and fat) to regenerate the myocardium and improve its functional status indicated that although the method appeared generally safe, its overall efficacy has remained modest. Several issues raised by these studies were notably related to the nature and number of injected cells, as well as the route and timing of their administration, to cite only a few. Besides the direct administration of cardiac precursor cells, a distinct approach to cardiac regeneration could be based upon the stimulation of the heart's natural ability to regenerate, using pharmacological approaches. Indeed, differentiation and/or proliferation of cardiac precursor cells is controlled by various endogenous mediators, such as growth factors and cytokines, which could thus be used as pharmacological agents to promote regeneration. To illustrate such approach, we present recent results showing that the exogenous administration of the natriuretic peptide BNP triggers “endogenous” cardiac regeneration, following experimental myocardial infarction. PMID:26880973

  20. Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor

    PubMed Central

    Wang, Xiaoqin; Xu, Weidong; Mohapatra, Subhra; Kong, Xiaoyuan; Li, Xu; Lockey, Richard F; Mohapatra, Shyam S

    2008-01-01

    Background Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally. Methods Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines. Results SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls. Conclusion These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma. PMID:18279512

  1. Salt-losing nephropathy associated with inappropriate secretion of atrial natriuretic peptide--a new clinical syndrome.

    PubMed

    Rodríguez-Soriano, J; Vallo, A

    1997-10-01

    A state of normokalemic renal sodium wasting associated with an apparently inappropriate secretion of atrial natriuretic peptide (ANP) has not been previously recognized. We here report an 11-year-old boy who presented with a chronic "salt-losing" nephropathy manifested by normonatremic or mildly hyponatremic extracellular fluid volume depletion, hypodipsia, absence of salt appetite, normokalemic metabolic alkalosis, hyper-reninemic hyperaldosteronism, hypertrophy of the juxtaglomerular apparatus, and highly conserved capacities for concentrating diluting the urine. Plasma ANP values were paradoxically elevated (between 10 and 47 fmol/ml), despite the coexistence of intravascular volume depletion and increased plasma levels of renin and aldosterone. Although the patient had some clinical similarities to Bartter's syndrome, fractional sodium chloride (NaCl) reabsorption during hypotonic saline diuresis was normal and no clinical amelioration was observed while on indomethacin therapy. Neither a tumor nor cardiac or cerebral abnormalities, which could be responsible for the increased ANP secretion, were detected. These clinical, biochemical, and histological features have not been previously described together and may represent a new clinical syndrome. The pathophysiology of this entity remains unknown, but an attractive, although unproven, hypothesis is that the renal defect in NaCl reabsorption in this patient could be related to an inappropriate and unregulated secretion of ANP.

  2. Atrial natriuretic peptide degradation by CPA47 cells - Evidence for a divalent cation-independent cell-surface proteolytic activity

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Chen, Y. M.; Whitson, P. A.

    1992-01-01

    Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88 percent of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41 percent of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

  3. Intracerebroventricular administration of C-type natriuretic peptide suppresses food intake via activation of the melanocortin system in mice.

    PubMed

    Yamada-Goto, Nobuko; Katsuura, Goro; Ebihara, Ken; Inuzuka, Megumi; Ochi, Yukari; Yamashita, Yui; Kusakabe, Toru; Yasoda, Akihiro; Satoh-Asahara, Noriko; Ariyasu, Hiroyuki; Hosoda, Kiminori; Nakao, Kazuwa

    2013-05-01

    C-type natriuretic peptide (CNP) and its receptor are abundantly distributed in the brain, especially in the arcuate nucleus (ARC) of the hypothalamus associated with regulating energy homeostasis. To elucidate the possible involvement of CNP in energy regulation, we examined the effects of intracerebroventricular administration of CNP on food intake in mice. The intracerebroventricular administration of CNP-22 and CNP-53 significantly suppressed food intake on 4-h refeeding after 48-h fasting. Next, intracerebroventricular administration of CNP-22 and CNP-53 significantly decreased nocturnal food intake. The increment of food intake induced by neuropeptide Y and ghrelin was markedly suppressed by intracerebroventricular administration of CNP-22 and CNP-53. When SHU9119, an antagonist for melanocortin-3 and melanocortin-4 receptors, was coadministered with CNP-53, the suppressive effect of CNP-53 on refeeding after 48-h fasting was significantly attenuated by SHU9119. Immunohistochemical analysis revealed that intracerebroventricular administration of CNP-53 markedly increased the number of c-Fos-positive cells in the ARC, paraventricular nucleus, dorsomedial hypothalamus, ventromedial hypothalamic nucleus, and lateral hypothalamus. In particular, c-Fos-positive cells in the ARC after intracerebroventricular administration of CNP-53 were coexpressed with α-melanocyte-stimulating hormone immunoreactivity. These results indicated that intracerebroventricular administration of CNP induces an anorexigenic action, in part, via activation of the melanocortin system.

  4. C-type natriuretic peptide prevents kidney injury and attenuates oxidative and inflammatory responses in hemorrhagic shock.

    PubMed

    Chen, Gan; Song, Xiang; Yin, Yujing; Xia, Sha; Liu, Qingjun; You, Guoxing; Zhao, Lian; Zhou, Hong

    2017-02-01

    Oxidative stress induced by hemorrhagic shock (HS) initiates a systemic inflammatory response, which leads to subsequent kidney injury. This study assessed the efficacy of c-type natriuretic peptide (CNP) in attenuating kidney injury in a rat model of hemorrhagic shock and resuscitation (HS/R). Sodium pentobarbital-anesthetized adult male Wistar rats underwent HS induced by the withdrawal of blood to a mean arterial pressure of 30-35 mmHg for 50 min. Then, the animals received CNP (25 μg/kg) or vehicle (saline) intravenously, followed byresuscitation with 1.5 times the shed blood volume in the form of normal saline. Mean arterial pressure was measured throughout the experiment, and acid-base status, oxidative stress, inflammation, tissue injury and kidney function were evaluated after resuscitation. CNP infusion reduced the malondialdehyde content, lowered the myeloperoxidase activity and decreased the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the kidney. The histologic injury score and the plasma creatinine concentration were also significantly decreased after CNP treatment compared to the vehicle group. CNP treatment ameliorates oxidative stress, the inflammatory response, and consequently acute kidney injury after HS/R. Thus, CNP may represent a promising strategy to improve resuscitation for the treatment of HS and deserves further investigation.

  5. Receptors for atrial natriuretic peptide (ANP) and regulation of thyroglobulin secretion by ANP in human thyroid cells

    SciTech Connect

    Sellitti, D.F.; Tseng, Y.C.L.; Wartofsky, L. Walter Reed Army Medical Center, Washington, DC )

    1989-01-01

    Specific binding sites for atrial natriuretic peptide (ANP) were identified and characterized in primary cultures of human thyroid cells. Saturation analysis using ({sup 125}I) {alpha} rat (1-28) ANP as the ligand showed a single class of high affinity binding which was inhibited by atriopeptin I and the {alpha} -human form of ANP, but not by a C-terminal fragment (13-28) of the peptide. The number of ANP binding sites in these cultures was not altered by the thyroid hormone concentration of the medium. In a dose-response experiment, thyroglobulin secretion was significantly reduced in the presence of 0.01 nM ANP and was maximally reduced with 10 nM ANP. Cyclic GMP production was increased threefold in the presence of 100 nM ANP, but was unchanged with lower doses of the peptides. The finding of receptors in thyroid follicular cells suggests a hitherto unrecognized role of ANP in the thyroid gland.

  6. An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes.

    PubMed

    Ruiz-Ojeda, Francisco Javier; Aguilera, Concepción María; Rupérez, Azahara Iris; Gil, Ángel; Gomez-Llorente, Carolina

    2016-08-15

    The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 μM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases.

  7. TEM studies of the effects of Zr additions on some HDDR-processed, high boron, NdFeB-type powders and hot-pressed magnets

    NASA Astrophysics Data System (ADS)

    Yi, G.; Chapman, J. N.; Brown, D. N.; Harris, I. R.

    2000-10-01

    The transmission electron microscope has been used to study the physical and magnetic microstructures of two HDDR-processed NdFeB-type alloys, one without Zr and the other containing 1.1 at% Zr. Studies were made of the as-produced powders and the solids produced following hot-pressing at 900°C. In the HDDR powders, the principal effects of adding Zr were to reduce the average grain size by ≈ {1}/{3} and made the grain size distribution more uniform. In the hot-pressed samples, the effect of Zr was more dramatic in that grain growth was very significantly reduced. Zr-containing phases were identified and a simple model, due to Zener, used to provide a plausible explanation of how the small amount of Zr present could stabilise the grain size to ≈0.5 μm. The microstructural results correlated well with measured magnetic properties.

  8. Influence of operation factors on brittle fracture initiation and critical local normal stress in SE(B) type specimens of VVER reactor pressure vessel steels

    NASA Astrophysics Data System (ADS)

    Kuleshova, E. A.; Erak, A. D.; Kiselev, A. S.; Bubyakin, S. A.; Bandura, A. P.

    2015-12-01

    A complex of mechanical tests and fractographic studies of VVER-1000 RPV SE(B) type surveillance specimens was carried out: the brittle fracture origins were revealed (non-metallic inclusions and structural boundaries) and the correlation between fracture toughness parameters (CTOD) and fracture surface parameters (CID) was established. A computational and experimental method of the critical local normal stress determination for different origin types was developed. The values of the critical local normal stress for the structural boundary origin type both for base and weld metal after thermal exposure and neutron irradiation are lower than that for initial state due to the lower cohesive strength of grain boundaries as a result of phosphorus segregation.

  9. Identification of cyst nematode B-type CLE peptides and modulation of the vascular stem cell pathway for feeding cell formation

    PubMed Central

    Guo, Xiaoli; Wang, Jianying; Fukuda, Hiroo; Kondo, Yuki; Wang, Xiaohong

    2017-01-01

    Stem cell pools in the SAM (shoot apical meristem), RAM (root apical meristem) and vascular procambium/cambium are regulated by CLE-receptor kinase-WOX signaling modules. Previous data showed that cyst nematode CLE-like effector proteins delivered into host cells through a stylet, act as ligand mimics of plant A-type CLE peptides and are pivotal for successful parasitism. Here we report the identification of a new class of CLE peptides from cyst nematodes with functional similarity to the B-type CLE peptide TDIF (tracheary element differentiation inhibitory factor) encoded by the CLE41 and CLE44 genes in Arabidopsis. We further demonstrate that the TDIF-TDR (TDIF receptor)-WOX4 pathway, which promotes procambial meristem cell proliferation, is involved in beet cyst nematode Heterodera schachtii parasitism. We observed activation of the TDIF pathway in developing feeding sites, reduced nematode infection in cle41 and tdr-1 wox4-1 mutants, and compromised syncytium size in cle41, tdr-1, wox4-1 and tdr-1 wox4-1 mutants. By qRT-PCR and promoter:GUS analyses, we showed that the expression of WOX4 is decreased in a clv1-101 clv2-101 rpk2-5 mutant, suggesting that WOX4 is a potential downstream target of nematode CLEs. Exogenous treatment with both nematode A-type and B-type CLE peptides induced massive cell proliferation in wild type roots, suggesting that the two types of CLEs may regulate cell proliferation during feeding site formation. These findings highlight an important role of the procambial cell proliferation pathway in cyst nematode feeding site formation. PMID:28158306

  10. During Cytochrome c Maturation CcmI Chaperones the Class I Apocytochromes until the Formation of Their b-Type Cytochrome Intermediates*

    PubMed Central

    Verissimo, Andreia F.; Shroff, Namita P.; Daldal, Fevzi

    2015-01-01

    The c-type cytochromes are electron transfer proteins involved in energy transduction. They have heme-binding (CXXCH) sites that covalently ligate heme b via thioether bonds and are classified into different classes based on their protein folds and the locations and properties of their cofactors. Rhodobacter capsulatus produces various c-type cytochromes using the cytochrome c maturation (Ccm) System I, formed from the CcmABCDEFGHI proteins. CcmI, a component of the heme ligation complex CcmFHI, interacts with the heme-handling protein CcmE and chaperones apocytochrome c2 by binding its C-terminal helix. Whether CcmI also chaperones other c-type apocytochromes, and the effects of heme on these interactions were unknown previously. Here, we purified different classes of soluble and membrane-bound c-type apocytochromes (class I, c2 and c1, and class II c′) and investigated their interactions with CcmI and apoCcmE. We report that, in the absence of heme, CcmI and apoCcmE recognized different classes of c-type apocytochromes with different affinities (nm to μm KD values). When present, heme induced conformational changes in class I apocytochromes (e.g. c2) and decreased significantly their high affinity for CcmI. Knowing that CcmI does not interact with mature cytochrome c2 and that heme converts apocytochrome c2 into its b-type derivative, these findings indicate that CcmI holds the class I apocytochromes (e.g. c2) tightly until their noncovalent heme-containing b-type cytochrome-like intermediates are formed. We propose that these intermediates are subsequently converted into mature cytochromes following the covalent ligation of heme via the remaining components of the Ccm complex. PMID:25979338

  11. Structure of Serum Albumin

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C.; Ho, Joseph X.

    1994-01-01

    Because of its availability, low cost, stability, and unusual ligand-binding properties, serum albumin has been one of the mst extensively studied and applied proteins in biochemistry. However, as a protein, albumin is far from typical, and the widespread interest in and application of albumin have not been balanced by an understanding of its molecular structure. Indeed, for more than 30 years structural information was surmised based solely on techniques such as hydrodynamics, low-angle X-ray scattering, and predictive methods.

  12. Usefulness of serum interleukin-18 in predicting cardiovascular mortality in patients with chronic kidney disease--systems and clinical approach.

    PubMed

    Formanowicz, Dorota; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Radom, Marcin; Formanowicz, Piotr

    2015-12-16

    The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2-year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non-diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory.

  13. Usefulness of serum interleukin-18 in predicting cardiovascular mortality in patients with chronic kidney disease – systems and clinical approach

    PubMed Central

    Formanowicz, Dorota; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Radom, Marcin; Formanowicz, Piotr

    2015-01-01

    The aim of this study was to check if serum interleukin-18 (IL-18) predicts 2-year cardiovascular mortality in patients at various stages of chronic kidney disease (CKD) and history of acute myocardial infarction (AMI) within the previous year. Diabetes mellitus was one of the key factors of exclusion. It was found that an increase in serum concentration of IL-18 above the cut-off point (1584.5 pg/mL) was characterized by 20.63-fold higher risk of cardiovascular deaths among studied patients. IL-18 serum concentration was found to be superior to the well-known cardiovascular risk parameters, like high sensitivity C-reactive protein (hsCRP), carotid intima media thickness (CIMT), glomerular filtration rate, albumins, ferritin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in prognosis of cardiovascular mortality. The best predictive for IL-18 were 4 variables, such as CIMT, NT-proBNP, albumins and hsCRP, as they predicted its concentration at 89.5%. Concluding, IL-18 seems to be important indicator and predictor of cardiovascular death in two-year follow-up among non-diabetic patients suffering from CKD, with history of AMI in the previous year. The importance of IL-18 in the process of atherosclerotic plaque formation has been confirmed by systems analysis based on a formal model expressed in the language of Petri nets theory. PMID:26669254

  14. The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors.

    PubMed

    Springer, Jeremy; Azer, John; Hua, Rui; Robbins, Courtney; Adamczyk, Andrew; McBoyle, Sarah; Bissell, Mary Beth; Rose, Robert A

    2012-05-01

    Natriuretic peptides (NPs) are best known for their ability to regulate blood vessel tone and kidney function whereas their electrophysiological effects on the heart are less clear. Here, we measured the effects of BNP and CNP on sinoatrial node (SAN) and atrial electrophysiology in isolated hearts as well as isolated SAN and right atrial myocytes from mice. BNP and CNP dose-dependently increased heart rate and conduction through the heart as indicated by reductions in R-R interval, P wave duration and P-R interval on ECGs. In conjunction with these ECG changes BNP and CNP (100 nM) increased spontaneous action potential frequency in isolated SAN myocytes by increasing L-type Ca(2+) current (I(Ca,L)) and the hyperpolarization-activated current (I(f)). BNP had no effect on right atrial myocyte APs in basal conditions; however, in the presence of isoproterenol (10nM), BNP increased atrial AP duration and I(Ca,L). Quantitative gene expression and immunocytochemistry data show that all three NP receptors (NPR-A, NPR-B and NPR-C) are expressed in the SAN and atrium. The effects of BNP and CNP on SAN and right atrial myocytes were maintained in mutant mice lacking functional NPR-C receptors and blocked by the NPR-A antagonist A71915 indicating that BNP and CNP function through their guanylyl cyclase-linked receptors. Our data also show that the effects of BNP and CNP are completely absent in the presence of the phosphodiesterase 3 inhibitor milrinone. Based on these data we conclude that NPs can increase heart rate and electrical conduction by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and inhibiting PDE3 activity.

  15. Present-day cosmic abundances. A comprehensive study of nearby early B-type stars and implications for stellar and Galactic evolution and interstellar dust models

    NASA Astrophysics Data System (ADS)

    Nieva, M.-F.; Przybilla, N.

    2012-03-01

    Context. Early B-type stars are ideal indicators for present-day cosmic abundances since they preserve their pristine abundances and typically do not migrate far beyond their birth environments over their short lifetimes, in contrast to older stars like the Sun. They are also unaffected by depletion onto dust grains, unlike the cold/warm interstellar medium (ISM) or H ii regions. Aims: A carefully selected sample of early B-type stars in OB associations and the field within the solar neighbourhood is studied comprehensively. Quantitative spectroscopy is used to characterise their atmospheric properties in a self-consistent way. Present-day abundances for the astrophysically most interesting chemical elements are derived in order to investigate whether a present-day cosmic abundance standard can be established. Methods: High-resolution and high-S/N FOCES, FEROS and ELODIE spectra of well-studied sharp-lined early B-type stars are analysed in non-LTE. Line-profile fits based on extensive model grids and an iterative analysis methodology are used to constrain stellar parameters and elemental abundances at high accuracy and precision. Atmospheric parameters are derived from the simultaneous establishment of independent indicators, from multiple ionization equilibria and the Stark-broadened hydrogen Balmer lines, and they are confirmed by reproduction of the stars' global spectral energy distributions. Results: Effective temperatures are constrained to 1-2% and surface gravities to less than 15% uncertainty, along with accurate rotational, micro- and macroturbulence velocities. Good agreement of the resulting spectroscopic parallaxes with those from the new reduction of the Hipparcos catalogue is obtained. Absolute values for abundances of He, C, N, O, Ne, Mg, Si and Fe are determined to better than 25% uncertainty. The synthetic spectra match the observations reliably over almost the entire visual spectral range. Three sample stars, γ Ori, o Per and θ1 Ori D, are

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

    PubMed

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

    2014-01-01

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

  17. Ammonia inhibits the C-type natriuretic peptide-dependent cyclic GMP synthesis and calcium accumulation in a rat brain endothelial cell line.

    PubMed

    Konopacka, Agnieszka; Zielińska, Magdalena; Albrecht, Jan

    2008-05-01

    Recently we reported a decrease of C-type natriuretic peptide (CNP)-dependent, natriuretic peptide receptor 2 (NPR2)-mediated cyclic GMP (cGMP) synthesis in a non-neuronal compartment of cerebral cortical slices of hyperammonemic rats [Zielińska, M., Fresko, I., Konopacka, A., Felipo, V., Albrecht, J., 2007. Hyperammonemia inhibits the natriuretic peptide receptor 2 (NPR2)-mediated cyclic GMP synthesis in the astrocytic compartment of rat cerebral cortex slices. Neurotoxicology 28, 1260-1263]. Here we accounted for the possible involvement of cerebral capillary endothelial cells in this response by measuring the effect of ammonia on the CNP-mediated cGMP formation and intracellular calcium ([Ca2+]i) accumulation in a rat cerebral endothelial cell line (RBE-4). We first established that stimulation of cGMP synthesis in RBE-4 cells was coupled to protein kinase G (PKG)-mediated Ca2+ influx from the medium which was inhibited by an L-type channel blocker nimodipine. Ammonia treatment (1h, 5mM NH4Cl) evoked a substantial decrease of CNP-stimulated cGMP synthesis which was related to a decreased binding of CNP to NPR2 receptors, and depressed the CNP-dependent [Ca2+]i accumulation in these cells. Ammonia also abolished the CNP-dependent Ca2+ accumulation in the absence of Na+. In cells incubated with ammonia in the absence of Ca2+ a slight CNP-dependent increase of [Ca2+]i was observed, most likely representing Ca2+ release from intracellular stores. Depression of CNP-dependent cGMP-mediated [Ca2+]i accumulation may contribute to cerebral vascular endothelial dysfunction associated with hyperammonemia or hepatic encephalopathy.

  18. The Denver Serum Bank.

    PubMed

    Eickhoff, Theodore C; Graves, Patricia S

    2015-10-01

    At the University of Colorado, Dr. Gordon Meiklejohn pursed the study of influenza and other respiratory pathogens for an unbroken period of 40 years, under the auspices of the Commission on Influenza of the Armed Forces Epidemiological Board through a series of contracts with the U.S. Army Medical Research and Development Command. Sera, throat washings, and other specimens for diagnosis were sent to Dr. Meiklejohn's laboratory. After serologic and virologic studies were carried out, aliquots of sera and virus samples were logged in and frozen. Sera were stored at -20°C and virus specimens at -70°C. These specimens became known as the Denver Serum Bank. The Bank supported military research programs and other researchers nationally and internationally until the 1990s when lacking of funding and considerations of administration, space, and cost resulted in the destruction of all specimens.

  19. SPITZER MID-IR SPECTRA OF DUST DEBRIS AROUND A AND LATE B TYPE STARS: ASTEROID BELT ANALOGS AND POWER-LAW DUST DISTRIBUTIONS

    SciTech Connect

    Morales, Farisa Y.; Werner, M. W.; Bryden, G.; Stapelfeldt, K. R.; Beichman, C. A.; Grogan, K.; Plavchan, P.; Rieke, G. H.; Su, K. Y. L.; Chen, C. H.; Kenyon, S. J.; Moro-Martin, A.; Wolf, S.

    2009-07-10

    Using the Spitzer/Infrared Spectrograph (IRS) low-resolution modules covering wavelengths from 5 to 35 {mu}m, we observed 52 main-sequence A and late B type stars previously seen using Spitzer/Multiband Imaging Photometer (MIPS) to have excess infrared emission at 24 {mu}m above that expected from the stellar photosphere. The mid-IR excess is confirmed in all cases but two. While prominent spectral features are not evident in any of the spectra, we observed a striking diversity in the overall shape of the spectral energy distributions. Most of the IRS excess spectra are consistent with single-temperature blackbody emission, suggestive of dust located at a single orbital radius-a narrow ring. Assuming the excess emission originates from a population of large blackbody grains, dust temperatures range from 70 to 324 K, with a median of 190 K corresponding to a distance of 10 AU. Thirteen stars however, have dust emission that follows a power-law distribution, F {sub {nu}} = F {sub 0}{lambda}{sup {alpha}}, with exponent {alpha} ranging from 1.0 to 2.9. The warm dust in these systems must span a greater range of orbital locations-an extended disk. All of the stars have also been observed with Spitzer/MIPS at 70 {mu}m, with 27 of the 50 excess sources detected (signal-to-noise ratio > 3). Most 70 {mu}m fluxes are suggestive of a cooler, Kuiper Belt-like component that may be completely independent of the asteroid belt-like warm emission detected at the IRS wavelengths. Fourteen of 37 sources with blackbody-like fits are detected at 70 {mu}m. The 13 objects with IRS excess emission fit by a power-law disk model, however, are all detected at 70 {mu}m (four above, three on, and six below the extrapolated power law), suggesting that the mid-IR IRS emission and far-IR 70 {mu}m emission may be related for these sources. Overall, the observed blackbody and power-law thermal profiles reveal debris distributed in a wide variety of radial structures that do not appear to be

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

    PubMed Central

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

    2011-01-01

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

  1. Four natriuretic peptides (ANP, BNP, VNP and CNP) coexist in the sturgeon: identification of BNP in fish lineage.

    PubMed

    Kawakoshi, A; Hyodo, S; Inoue, K; Kobayashi, Y; Takei, Y

    2004-04-01

    The natriuretic peptide (NP) family is composed of three members: atrial, brain/ventricular and C-type NPs (ANP, BNP/VNP and CNP respectively) in tetrapods and teleostean fish, but only CNP in elasmobranch fish. In order to trace the process of divergence of the NP family in early vertebrate evolution, we attempted to detect NPs in the primitive ray-finned fish, the sturgeon (Acipenser transmontanus). Unexpectedly, we isolated four distinct NP cDNAs from the heart and brain of this chondrostean fish. The single NP from the brain was CNP, as judged from the lack of C-terminal 'tail' sequence extending from the intramolecular ring. Two of the three cardiac NPs were ANP and VNP, as judged by the presence of an amidation signal at its C-terminus (ANP) and a long and conserved C-terminal tail sequence (VNP) respectively. The third cardiac NP was most probably BNP because it possessed all the features characteristic of BNP including: (1) the presence of dibasic amino acids within the intramolecular ring; (2) the presence of AUUUA repeats in the 3'-untranslated region of its mRNA; (3) equivalent expression of its mRNA in the atrium and ventricle and appreciable expression in the brain. Based on the sturgeon BNP sequence, we further isolated BNP cDNA from the heart of tilapia and pufferfish for the first time in teleostean fish. Phylogenetic analysis of the precursors showed that newly identified NPs belong to each group of the four NPs. The current identification of both VNP and BNP in the sturgeon clearly showed that BNP and VNP are coded by distinct genes, and that the NP family consists of at least four members in the ray-finned fish. VNP has not been molecularly identified in mammals but its presence is suggested from physiological studies; heterologous fish VNP exhibited more potent vasorelaxant activity than homologous mammalian ANP in the isolated coronary artery of dogs.

  2. Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

    PubMed Central

    Adnot, S; Andrivet, P; Chabrier, P E; Piquet, J; Plas, P; Braquet, P; Roudot-Thoraval, F; Brun-Buisson, C

    1989-01-01

    To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD. PMID:2522105

  3. Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers

    PubMed Central

    Gupta, Rajinder K.; Himashree, G.; Singh, Krishan; Soree, Poonam; Desiraju, Koundinya; Agrawal, Anurag; Ghosh, Dishari; Dass, Deepak; Reddy, Prassana K.; Panjwani, Usha; Singh, Shashi Bala

    2016-01-01

    Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility. PMID:26892302

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

    PubMed Central

    Broderick, Tom L; Jankowski, Marek; Gutkowska, Jolanta

    2017-01-01

    Background Regular exercise training (ET) and caloric restriction (CR) are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT)–natriuretic peptide (NP) system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity. Methods Five-week-old male db/db mice were assigned to the following groups: sedentary, ET, and ET + CR. Nonobese heterozygote littermates served as controls. ET was performed on a treadmill at moderate intensity, and CR was induced by reducing food intake by 30% of that consumed by sedentary db/db mice for a period of 8 weeks. Results After 8 weeks, only ET + CR, but not ET, slightly improved body weight compared to sedentary db/db mice. Regardless of the treatment, db/db mice remained hyperglycemic. Hearts from db/db mice demonstrated reduced expression of genes linked to the cardiac OT–NP system. In fact, compared to control mice, mRNA expression of GATA binding protein 4 (GATA4), OT receptor, OT, brain NP, NP receptor type C, and endothelial nitric oxide synthase (eNOS) was decreased in hearts from sedentary db/db mice. Both ET alone and ET + CR increased the mRNA expression of GATA4 compared to sedentary db/db mice. Only ET combined with CR produced increased eNOS mRNA and protein expression. Conclusion Our data indicate that enhancement of eNOS by combined ET and CR may improve coronary endothelial vasodilator dysfunction in type 2 diabetes but did not prevent the downregulation of cardiac expression in the OT–NP system, possibly resulting from the sustained hyperglycemia and obesity in diabetic mice. PMID:28138261

  5. Tissue Doppler imaging and plasma N-terminal probrain natriuretic peptide for the identification of hypertrophic cardiomyopathy mutation carriers.

    PubMed

    Silva, Doroteia; Madeira, Hugo; Almeida, Augusto; Brito, Dulce

    2013-10-01

    Previous studies have shown that tissue Doppler imaging (TDI) is able to identify mutation carriers of hypertrophic cardiomyopathy (HC) before the development of the clinical phenotype. However, data are scarce and have sometimes been controversial. We performed a systematic study that included conventional echocardiography, TDI, and plasma NT-probrain natriuretic peptide (NT-proBNP) measurement to evaluate the parameters that could identify HC mutation carriers. A total of 138 genotyped subjects were included and divided into 3 groups: group 1, those with HC (n = 62); group 2, mutation carriers (first-degree relatives with a positive genotype but negative phenotype; n = 34); and group 3, controls (first-degree relatives with a negative genotype and phenotype; n = 42). An echocardiographic study, including TDI, was performed on all subjects, and a TDI-derived index (global function index) was also determined. The age-adjusted mean differences in the echocardiographic and TDI parameters and NT-proBNP levels were compared among the 3 groups. Compared with the HC group, the carriers had significantly higher mean E' velocities, lower mean E/E' ratio, higher mean S' velocities, and lower mean global function index and NT-proBNP values. The carriers and controls did not differ significantly either in the echocardiographic parameters studied or in the NT-proBNP levels. In conclusion, the echocardiographic and TDI parameters and NT-proBNP levels cannot be used to identify the HC mutation carrier state and therefore do not appear to be reliable for the purpose of making a preclinical diagnosis of the disease.

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

    PubMed Central

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

    2015-01-01

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

  7. Non-linear Equation using Plasma Brain Natriuretic Peptide Levels to Predict Cardiovascular Outcomes in Patients with Heart Failure

    PubMed Central

    Fukuda, Hiroki; Suwa, Hideaki; Nakano, Atsushi; Sakamoto, Mari; Imazu, Miki; Hasegawa, Takuya; Takahama, Hiroyuki; Amaki, Makoto; Kanzaki, Hideaki; Anzai, Toshihisa; Mochizuki, Naoki; Ishii, Akira; Asanuma, Hiroshi; Asakura, Masanori; Washio, Takashi; Kitakaze, Masafumi

    2016-01-01

    Brain natriuretic peptide (BNP) is the most effective predictor of outcomes in chronic heart failure (CHF). This study sought to determine the qualitative relationship between the BNP levels at discharge and on the day of cardiovascular events in CHF patients. We devised a mathematical probabilistic model between the BNP levels at discharge (y) and on the day (t) of cardiovascular events after discharge for 113 CHF patients (Protocol I). We then prospectively evaluated this model on another set of 60 CHF patients who were readmitted (Protocol II). P(t|y) was the probability of cardiovascular events occurring after >t, the probability on t was given as p(t|y) = −dP(t|y)/dt, and p(t|y) = pP(t|y) = αyβP(t|y), along with p = αyβ (α and β were constant); the solution was p(t|y) = αyβ exp(−αyβt). We fitted this equation to the data set of Protocol I using the maximum likelihood principle, and we obtained the model p(t|y) = 0.000485y0.24788 exp(−0.000485y0.24788t). The cardiovascular event-free rate was computed as P(t) = 1/60Σi=1,…,60 exp(−0.000485yi0.24788t), based on this model and the BNP levels yi in a data set of Protocol II. We confirmed no difference between this model-based result and the actual event-free rate. In conclusion, the BNP levels showed a non-linear relationship with the day of occurrence of cardiovascular events in CHF patients. PMID:27845390

  8. Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

    PubMed Central

    Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Elesgaray, Rosana; Laughlin, Myriam Mac; Tomat, Analía; Arranz, Cristina; Costa, Maria A.

    2013-01-01

    Introduction The aim of this study was to investigate both the effects of chronic treatment with atrial natriuretic peptide (ANP) on systolic blood pressure (SBP), cardiac nitric oxide (NO) system, oxidative stress, hypertrophy, fibrosis and apoptosis in spontaneously hypertensive rats (SHR), and sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/hr/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). SBP was recorded and nitrites and nitrates excretion (NOx) were determined. After treatment, NO synthase (NOS) activity, eNOS expression, thiobarbituric acid-reactive substances (TBARS) and glutathione concentration were determined in left ventricle, as well as the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). Morphological studies in left ventricle were performed in slices stained with hematoxylin-eosin or Sirius red to identify collagen as a fibrosis indicator; immunohistochemistry was employed for identification of transforming growth factor beta; and apoptosis was evaluated by Tunel assay. Results Female SHR showed lower SBP, higher NO-system activity and less oxidative stress, fibrosis and hypertrophy in left ventricle, as well as higher cardiac NOS activity, eNOS protein content and NOx excretion than male SHR. Although ANP treatment lowered blood pressure and increased NOS activity and eNOS expression in both sexes, cardiac NOS response to ANP was more marked in females. In left ventricle, ANP reduced TBARS and increased glutathione concentration and activity of CAT and SOD enzymes in both sexes, as well as GPx activity in males. ANP decreased fibrosis and apoptosis in hearts from male and female SHR but females showed less end-organ damage in heart. Chronic ANP treatment would ameliorate hypertension and end-organ damage in heart by reducing oxidative stress, increasing NO-system activity, and diminishing fibrosis and

  9. Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet

    PubMed Central

    Della Penna, Silvana Lorena; Cao, Gabriel; Carranza, Andrea; Zotta, Elsa; Gorzalczany, Susana; Cerrudo, Carolina Susana; Rukavina Mikusic, Natalia Lucía; Correa, Alicia; Trida, Verónica; Toblli, Jorge Eduardo; Fernández, Belisario Enrique

    2014-01-01

    In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1α is involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1α compared to their control. These findings suggest that HIF-1α and ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis. PMID:24689065

  10. Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos.

    PubMed Central

    Kovacic-Milivojević, B; Gardner, D G

    1992-01-01

    Employing transient transfection analysis in neonatal rat cardiocytes, we have demonstrated that overexpression of c-jun results in a dose-dependent induction of the human atrial natriuretic peptide (hANP) gene promoter. Studies using a series of mutations in the hANP gene promoter identified a TRE-like, cis-acting regulatory sequence which conferred c-jun sensitivity. This same region was shown to interact with the c-jun/c-fos complex in an in vitro gel mobility shift assay. Selective mutation of this site suppressed basal activity of the hANP promoter and significantly reduced c-jun-dependent activation. Overexpression of c-fos had a biphasic effect on hANP gene promoter activity. At low levels, in concert with c-jun, it activated, while at higher levels it suppressed, transcription from the hANP gene promoter. This inhibition was both cell and promoter specific. hANP gene promoter sequences which mediate c-fos-dependent inhibition appear to be separable from those responsible for the induction. In addition, the protein domains on c-fos responsible for transcriptional activation and repression can be segregated topographically, with the inhibitory activity being localized to the carboxy-terminal domain. Thus, c-fos can activate or repress hANP gene expression through two separate functional domains that act on distinct regulatory elements in the hANP gene promoter. These data imply that the ANP gene may be a physiological target for c-fos- and c-jun-dependent activity in the heart and suggest a potential mechanism linking environmental stimuli to its expression. Images PMID:1530876

  11. Brain natriuretic peptide as a potential novel marker of salt-sensitivity in chronic kidney disease patients without cardiac dysfunction.

    PubMed

    Hayashi, Mutsuharu; Yasuda, Yoshinari; Suzuki, Susumu; Tagaya, Manaka; Ito, Takehiro; Kamada, Tomohito; Yoshinaga, Masataka; Sugishita, Yoshinori; Fujiwara, Wakaya; Yokoi, Hiroatsu; Ozaki, Yukio; Izawa, Hideo

    2017-03-01

    Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.

  12. Non-linear Equation using Plasma Brain Natriuretic Peptide Levels to Predict Cardiovascular Outcomes in Patients with Heart Failure

    NASA Astrophysics Data System (ADS)

    Fukuda, Hiroki; Suwa, Hideaki; Nakano, Atsushi; Sakamoto, Mari; Imazu, Miki; Hasegawa, Takuya; Takahama, Hiroyuki; Amaki, Makoto; Kanzaki, Hideaki; Anzai, Toshihisa; Mochizuki, Naoki; Ishii, Akira; Asanuma, Hiroshi; Asakura, Masanori; Washio, Takashi; Kitakaze, Masafumi

    2016-11-01

    Brain natriuretic peptide (BNP) is the most effective predictor of outcomes in chronic heart failure (CHF). This study sought to determine the qualitative relationship between the BNP levels at discharge and on the day of cardiovascular events in CHF patients. We devised a mathematical probabilistic model between the BNP levels at discharge (y) and on the day (t) of cardiovascular events after discharge for 113 CHF patients (Protocol I). We then prospectively evaluated this model on another set of 60 CHF patients who were readmitted (Protocol II). P(t|y) was the probability of cardiovascular events occurring after >t, the probability on t was given as p(t|y) = ‑dP(t|y)/dt, and p(t|y) = pP(t|y) = αyβP(t|y), along with p = αyβ (α and β were constant); the solution was p(t|y) = αyβ exp(‑αyβt). We fitted this equation to the data set of Protocol I using the maximum likelihood principle, and we obtained the model p(t|y) = 0.000485y0.24788 exp(‑0.000485y0.24788t). The cardiovascular event-free rate was computed as P(t) = 1/60Σi=1,…,60 exp(‑0.000485yi0.24788t), based on this model and the BNP levels yi in a data set of Protocol II. We confirmed no difference between this model-based result and the actual event-free rate. In conclusion, the BNP levels showed a non-linear relationship with the day of occurrence of cardiovascular events in CHF patients.

  13. Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery.

    PubMed

    Marrachelli, Vannina G; Centeno, José M; Miranda, Ignacio; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Miranda, Francisco J; Alborch, Enrique

    2012-11-01

    Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal decreased the ANP-induced relaxation but inhibition of NO-synthesis did not modify ANP-induced relaxations. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium (TEA) partly inhibited the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to ANP, and these inhibitions were lower in diabetic than in control rabbits. Indomethacin potentiated the relaxation to ANP, more in control than in diabetic rabbits. In the presence of ANP the renal artery released thromboxane A(2) and prostacyclin, and the release of prostacyclin resulted decreased in diabetic rabbits. The present results suggest that diabetes produces hyporeactivity of the rabbit renal artery to ANP by mechanisms that at least include the reduced modulation by prostacyclin and a lower participation of ATP-sensitive K(+) channel (K(ATP)), voltage-sensitive K(+) channels (K(V)) and TEA-sensitive K(+) channels (K(Ca)).

  14. Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a 'whip-brake' system of the endocrine heart.

    PubMed

    Tota, Bruno; Cerra, Maria Carmela; Gattuso, Alfonsina

    2010-09-15

    In the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and release catecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981 with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as major cardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic and therapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiac hormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A (CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in 'zero steady-state error' homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence for the hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to organize 'whip-brake' connection-integration processes in spatio-temporal networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The use of fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components of cardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, or under stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networks and how they have evolved from relatively less complicated designs. The latter can also be used

  15. Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System.

    PubMed

    Ventura, Nicole M; Li, Terry Y; Tse, M Yat; Andrew, R David; Tayade, Chandrakant; Jin, Albert Y; Pang, Stephen C

    2015-12-01

    Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP(-/-)) exhibit a gestational hypertensive phenotype. In the current study, female ANP(+/+) and ANP(-/-) mice were mated with ANP(+/+) males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP(+/+) and ANP(-/-) dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT(1a) genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy.

  16. A prospective study of brain natriuretic peptide levels in three subgroups: Stroke with hypertension, stroke without hypertension, and hypertension alone

    PubMed Central

    Cakir, Zeynep; Saritas, Ayhan; Emet, Mucahit; Aslan, Sahin; Akoz, Ayhan; Gundogdu, Fuat

    2010-01-01

    Aim: To study brain natriuretic peptide (BNP) levels in three subgroups: patients having stroke with hypertension (HT), those having stroke without HT, and those with HT alone. We also tried to identify whether BNP levels predict the length of stay in hospital and mortality. Materials and Methods: The groups were formed by patients who had been admitted to the emergency department in the first 4–12 h after the onset of symptoms. There were 30 stroke patients with a history of HT (group I), 30 stroke patients without a history of HT (group II), and 20 HT patients without stroke (group III). Patients with congestive heart failure, chronic cor pulmonale, severe valvular heart disease, chronic renal failure, liver insufficiency, diabetes mellitus, atrial fibrillation, and those with a history of stroke were excluded from the study since these diseases can affect the plasma BNP levels. Results: The demographic characteristics, except the age distribution, were similar among the groups. The mean BNP levels in the three groups were 168.8 ± 223.9 pg/ml, 85.0 ± 75.1 pg/ml, and 84.8 ± 178.3 pg/ml, respectively. The differences between the groups were statistically significant. Conclusion: The mean BNP levels were affected by HT and/or stroke. The simultaneous presence of HT and stroke results in a more significant increase BNP than the presence of either stroke or HT alone. When diseases that can affect the plasma BNP levels are excluded, the BNP levels in stroke patients without a history of HT are similar to the levels seen in patients with only HT. PMID:20436747

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

    PubMed

    Lin, Jing; Han, Zhenhui; Li, Hongxia; Chen, Selena Ying; Li, Xueying; Liu, Ping; Wang, Yuli; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2015-01-01

    POTS is a global public-health disease, but predictor for therapeutic response to metoprolol in children with POTS is lacking. This study was designed to investigate predictive value of plasma C-type natriuretic peptide (CNP) in the therapeutic efficacy of metoprolol on postural tachycardia syndrome (POTS) in children. Totally 34 children with POTS and 27 healthy children were included in the study. The head-up test or head-up tilt test was used to check heart rate and blood pressure from supine to upright in subjects. A double antibody (competitive) sandwich immunoluminometric assay was used to detect plasma CNP. Metoprolol was used to treat children with POTS. The difference in plasma concentrations of CNP between responders and non-responders was compared. An ROC curve was used to analyze plasma CNP to predict efficacy of metoprolol on POTS in children. Plasma CNP in children with POTS was significantly higher than that of healthy children [(51.9 ± 31.4) vs. (25.1 ± 19.1) pg/ml, P <0.001]. Plasma CNP in responders to metoprolol was significantly higher than non-responders [(59.1 ± 33.5) vs. (34.8 ± 16.7) pg/ml, P = 0.037] before treatment. The ROC curve showed that area under the curve was 0.821 (95% CI 0.642-0.999). The cut-off value of plasma CNP > 32.55 pg/ml yielded a sensitivity of 95.8% and specificity of 70% in predicting therapeutic efficacy of metoprolol on POTS children. Plasma CNP might serve as a useful predictor for the therapeutic efficacy of metoprolol on POTS in children.

  18. Hypergravity differentially modulates cGMP efflux in human melanocytic cells stimulated by nitric oxide and natriuretic peptides

    NASA Astrophysics Data System (ADS)

    Ivanova, K.; Stieber, C.; Lambers, B.; Block, I.; Krieg, R.; Wellmann, A.; Gerzer, R.

    Nitric oxide NO plays a key role in many patho physiologic processes including inflammation and skin cancer The diverse cellular effects of NO are mainly mediated by activation of the soluble guanylyl cyclase sGC isoform that leads to increases in intracellular cGMP levels whereas the membrane-bound isoforms serve as receptors for natriuretic peptides e g ANP In human skin epidermal melanocytes represent the principal cells for skin pigmentation by synthesizing the pigment melanin Melanin acts as a scavenger for free radicals that may arise during metabolic stress as a result of potentially harmful effects of the environment In previous studies we found that long-term exposure to hypergravity stimulated cGMP efflux in normal human melanocytes NHMs and non-metastatic melanoma cells at least partly by an enhanced expression of the multidrug resistance proteins MRP and cGMP transporters MRP4 5 The present study investigated whether hypergravity generated by centrifugal acceleration may modulate the cGMP efflux in NO-stimulated NHMs and melanoma cells MCs with different metastatic potential The NONOates PAPA-NO and DETA-NO were used as direct NO donors for cell stimulation In the presence of 0 1 mM DETA-NO t 1 2 sim 20 h long-term application of hypergravity up to 5 g for 24 h reduced intracellular cGMP levels by stimulating cGMP efflux in NHMs and non-metastatic MCs in comparison to 1 g whereas exposure to 5 g for 6 h in the presence of 0 1 mM PAPA-NO t 1 2 sim 30 min was not effective The hypergravity-stimulated

  19. Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight.

    PubMed

    Engle, Steven K; Watson, David E

    2016-02-01

    Cardiovascular (CV) toxicity is an important cause of failure during drug development. Blood-based biomarkers can be used to detect CV toxicity during preclinical development and prioritize compounds at lower risk of causing such toxicities. Evidence of myocardial degeneration can be detected by measuring concentrations of biomarkers such as cardiac troponin I and creatine kinase in blood; however, detection of functional changes in the CV system, such as blood pressure, generally requires studies in animals with surgically implanted pressure transducers. This is a significant limitation because sustained changes in blood pressure are often accompanied by changes in heart rate and together can lead to cardiac hypertrophy and myocardial degeneration in animals, and major adverse cardiovascular events (MACE) in humans. Increased concentrations of NPs in blood correlate with higher risk of cardiac mortality, all-cause mortality, and MACE in humans. Their utility as biomarkers of CV function and toxicity in rodents was investigated by exploring the relationships between plasma concentrations of NTproANP and NTproBNP, blood pressure, heart rate, and heart weight in Sprague Dawley rats administered compounds that caused hypotension or hypertension, including nifedipine, fluprostenol, minoxidil, L-NAME, L-thyroxine, or sunitinib for 1-2 weeks. Changes in NTproANP and/or NTproBNP concentrations were inversely correlated with changes in blood pressure. NTproANP and NTproBNP concentrations were inconsistently correlated with relative heart weights. In addition, increased heart rate was associated with increased heart weights. These studies support the use of natriuretic peptides and heart rate to detect changes in blood pressure and cardiac hypertrophy in short-duration rat studies.

  20. One-year prognosis and the role of brain natriuretic peptide levels in patients with chronic cor pulmonale.

    PubMed

    Park, So Young; Lee, Chang Youl; Kim, Changhwan; Jang, Seung Hun; Park, Yong Bum; Park, Sunghoon; Hwang, Yong Il; Lee, Myung Goo; Jung, Ki-Suck; Kim, Dong-Gyu

    2015-04-01

    Data on the clinical outcomes and role of brain natriuretic peptide (BNP) levels in patients with chronic cor pulmonale are limited. A total of 69 patients with chronic cor pulmonale, admitted for dyspnea (January 2007 to September 2011) to three university hospitals, were retrospectively reviewed. All of the patients had right ventricular (RV) dysfunction on echocardiography. The median age was 70.0 yr, and chronic obstructive pulmonary disease (40.6%) and tuberculosis-destroyed lung (TDL, 27.5%) were the leading causes of chronic cor pulmonale. At the 1-yr follow-up, the mortality rate was 15.9%, and the readmission rate was 53.7%; patients with TDL had higher mortality (31.6% vs. 10.0%; P=0.059) and readmission rates (78.9% vs. 43.8%; P=0.009) than those with non-TDL diseases. The area under the receiver operating characteristic curve for admission BNP levels to predict readmission was 0.788 (95% confidence interval [CI], 0.673-0.904), and the sensitivity and specificity of the cut-off value were 80.6% and 77.4%, respectively. In multivariate analysis, high admission BNP levels were a significant risk factor for subsequent readmission (hazard ratio, 1.049; 95% CI, 1.005-1.094). Additionally, admission BNP levels were well correlated with cardiac troponin I (r=0.558), and delta BNP also correlated with delta RV systolic pressure (n=25; r=0.562). In conclusion, among hospitalized patients with chronic cor pulmonale, admission high BNP levels are a significant risk factor for subsequent readmission. Therefore, more intensive monitoring and treatment are needed in patients with higher BNP levels.

  1. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes

    PubMed Central

    Bordicchia, Marica; Liu, Dianxin; Amri, Ez-Zoubir; Ailhaud, Gerard; Dessì-Fulgheri, Paolo; Zhang, Chaoying; Takahashi, Nobuyuki; Sarzani, Riccardo; Collins, Sheila

    2012-01-01

    The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of “brown adipocytes” within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional “brown-like” adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK–dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C–/– mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote “browning” of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology. PMID:22307324

  2. The A- and B-type cyclins of Drosophila are accumulated and destroyed in temporally distinct events that define separable phases of the G2-M transition.

    PubMed Central

    Whitfield, W G; Gonzalez, C; Maldonado-Codina, G; Glover, D M

    1990-01-01

    We show that the sequence of Drosophila cyclin B has greater identity with B-type cyclins from other animal phyla than with Drosophila cyclin A, suggesting that the two cyclins have distinct roles that have been maintained in evolution. Cyclin A is not detectable in unfertilized eggs and is present at low levels prior to cellularization of the syncytial embryo. In contrast, the levels of cyclin B remain uniformly high throughout these developmental stages. In cells within cellularized embryos and the larval brain, cyclin A accumulates to peak levels in prophase and is degraded throughout the period in which chromosomes are becoming aligned on the metaphase plate. The degradation of cyclin B, on the other hand, does not occur until the metaphase-anaphase transition. In cells arrested at c-metaphase by treating with microtubule destabilizing drugs to prevent spindle formation, cyclin A has been degraded in the arrested cells, whereas cyclin B is maintained at high levels. These observations suggest that cyclin A has a role in the G2-M transition that is independent of spindle formation, and that entry into anaphase is a key requirement for the degradation of cyclin B. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:2142452

  3. The role of nonmagnetic d0 vs. d10B-type cations on the magnetic exchange interactions in osmium double perovskites

    NASA Astrophysics Data System (ADS)

    Feng, Hai L.; Yamaura, Kazunari; Tjeng, Liu Hao; Jansen, Martin

    2016-11-01

    Polycrystalline samples of double perovskites Ba2BOsO6 (B=Sc, Y, In) were synthesized by solid state reactions. They adopt the cubic double perovskite structures (space group, Fm-3m) with ordered B and Os arrangements. Ba2BOsO6 (B=Sc, Y, In) show antiferromagnetic transitions at 93 K, 69 K, and 28 K, respectively. The Weiss-temperatures are -590 K for Ba2ScOsO6, -571 K for Ba2YOsO6, and -155 K for Ba2InOsO6. Sc3+ and Y3+ have the open-shell d0 electronic configuration, while In3+ has the closed-shell d10. This indicates that a d0 B-type cation induces stronger overall magnetic exchange interactions in comparison to a d10. Comparison of Ba2BOsO6 (B=Sc, Y, In) to their Sr and Ca analogues shows that the structural distortions weaken the overall magnetic exchange interactions.

  4. Chronic psychosocial stress in male mice causes an up-regulation of scavenger receptor class B type 1 protein in the adrenal glands.

    PubMed

    Füchsl, Andrea M; Uschold-Schmidt, Nicole; Reber, Stefan O

    2013-07-01

    Mice exposed to chronic subordinate colony housing (CSC, 19 days) show an exaggerated adrenal corticosterone response to an acute heterotypic stressor (elevated platform (EPF), 5 min) despite no difference from EPF-exposed single-housed control (SHC) mice in corticotropin (ACTH) secretion. In the present study, we asked the question whether this CSC-induced increase in adrenal capability to produce and secrete corticosterone is paralleled by an enhanced adrenal availability and/or mobilization capacity of the corticosterone precursor molecule cholesterol. Employing oil-red staining and western blot analysis we revealed comparable relative density of cortical lipid droplets and relative protein expression of hormone-sensitive lipase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density lipoprotein receptor (LDL-R) between CSC and SHC mice. However, relative protein expression of the scavenger receptor class B type 1 (SR-BI) was increased following CSC exposure. Moreover, analysis of plasma high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) revealed increased LDL-C levels in CSC mice. Together with the pronounced increase in adrenal weight, evidently mediated by hyperplasia of adrenocortical cells, these data strongly indicate an enhanced adrenal availability of and capacity to mobilize cholesterol in chronic psychosocially-stressed mice, contributing to their increased in vivo corticosterone response during acute heterotypic stressor exposure.

  5. Commercial-scale recycling of NdFeB-type magnets with grain boundary modification yields products with 'designer properties' that exceed those of starting materials.

    PubMed

    Zakotnik, M; Tudor, C O

    2015-10-01

    NdFeB-type magnets dominate the market for high performance magnetic materials, yet production of 'virgin' magnets via mining is environmentally, financially and energetically costly. Hence, interest is growing in 'magnet to magnet' recycling schemes that offer the potential for cheaper, more environmentally-friendly solutions to the world's growing appetite for rare-earth based magnetic materials. Unfortunately, previously described recycling processes only partially capitalise on this potential, because the methods described to date are limited to 'laboratory scale' or operate only under ideal conditions and result in products that fail to recapture the coercivity of the starting, scrap materials. Herein, we report a commercial scale process (120 kg batches) that completely recovers the properties of the starting scrap magnets. Indeed, 'grain boundary modification', via careful addition of a proprietary mix of blended elements, produces magnets with 'designer properties' that can exceed those of the starting materials and can be closely tailored to meet a wide variety of end-user applications, including high-coercivity (>2000 kA/m), sintered magnets suitable for motor applications.

  6. Periodic wave, breather wave and travelling wave solutions of a (2 + 1)-dimensional B-type Kadomtsev-Petviashvili equation in fluids or plasmas

    NASA Astrophysics Data System (ADS)

    Hu, Wen-Qiang; Gao, Yi-Tian; Jia, Shu-Liang; Huang, Qian-Min; Lan, Zhong-Zhou

    2016-11-01

    In this paper, a (2 + 1)-dimensional B-type Kadomtsev-Petviashvili equation is investigated, which has been presented as a model for the shallow water wave in fluids or the electrostatic wave potential in plasmas. By virtue of the binary Bell polynomials, the bilinear form of this equation is obtained. With the aid of the bilinear form, N -soliton solutions are obtained by the Hirota method, periodic wave solutions are constructed via the Riemann theta function, and breather wave solutions are obtained according to the extended homoclinic test approach. Travelling waves are constructed by the polynomial expansion method as well. Then, the relations between soliton solutions and periodic wave solutions are strictly established, which implies the asymptotic behaviors of the periodic waves under a limited procedure. Furthermore, we obtain some new solutions of this equation by the standard extended homoclinic test approach. Finally, we give a generalized form of this equation, and find that similar analytical solutions can be obtained from the generalized equation with arbitrary coefficients.

  7. Cholesterol depletion induces PKA-mediated basolateral-to-apical transcytosis of the scavenger receptor class B type I in MDCK cells

    PubMed Central

    Burgos, Patricia V.; Klattenhoff, Carla; de la Fuente, Erwin; Rigotti, Attilio; González, Alfonso

    2004-01-01

    Cholesterol-based membrane microdomains, or lipid rafts, are believed to play important, yet poorly defined, roles in protein trafficking and signal transduction. In polarized epithelial cells, the current view is that rafts are involved in apical but not in basolateral protein transport from the trans-Golgi network (TGN). We report here that cholesterol is required in a post-TGN mechanism of basolateral regionalization. Permanently transfected Madin-Darby canine kidney cells segregated the caveolae/raft-associated high-density lipoprotein scavenger receptor class B type I (SR-BI) predominantly to the basolateral domain where it was constitutively internalized and recycled basolaterally. Acute cholesterol depletion did not significantly alter SR-BI internalization, implying a cholesterol depletion-insensitive endocytic process but instead induced its transcytosis through a protein kinase A (PKA)- and microtubule-dependent mechanism. Forskolin also elicited SR-BI transcytosis. The basolateral distribution of endogenous epidermal growth factor receptor remained unaffected. Strikingly, cholesterol depletion induced PKA activity without increasing the cAMP levels. Thus, our results are consistent with a scenario in which cholesterol-based rafts promote internalization and basolateral recycling of internalized SR-BI whereas a PKA pool sensitive to cholesterol depletion mediates SR-BI transcytosis. Regulated transcytosis of SR-BI may provide an additional mechanism to control cholesterol homeostasis. These results disclose relationships between cholesterol-based rafts and PKA activity operating in a post-TGN mechanism of regulated apical-to-basolateral cell surface protein distribution. PMID:15007173

  8. Silencing of the scavenger receptor (Class B - Type 1) gene using siRNA-loaded chitosan nanaoparticles in a HepG2 cell model.

    PubMed

    Farid, Mariane M; Hathout, Rania M; Fawzy, Mahmoud; Abou-Aisha, Khaled

    2014-11-01

    Gene silencing mediated by small interfering RNA (siRNA) has gained increasing interest through the past few decades. However, the partial negative charge and the susceptibility to degradation by nucleases have hampered its use in a naked form. In this study, we investigated the use of chitosan nanoparticles as non-viral delivery carriers of siRNA. As a model target, we selected the scavenger receptor (SR-B1), due to its proposed involvement in hepatitis C virus (HCV) internalization. Low molecular weight (LMW) chitosan nanoparticles were prepared by simple ionic gelation using sodium tripolyphosphate (TPP) as a cross-linking agent; a fixed chitosan and TPP concentration of 0.1% was used, and a chitosan to TPP weight ratios of 3:1, 5:1, and 9:1 were investigated. Nanoparticle uptake efficiency was measured using FITC-labeled chitosan nanoparticles and silencing of scavenger receptor class B type 1 (SR-B1) in HepG2 cell line was tested using Western blot analysis. Nanoparticles produced were spherical in shape with an optimum particle size and distribution. The uptake of FITC-labeled nanoparticles by HepG2 cells was found to be both concentration and time dependent. Furthermore, Western Blot analysis showed that SR-B1 siRNA was able to silence the scavenger receptor for up to 96 h of incubation with HepG2 cells.

  9. Caenorhabditis elegans P5B-type ATPase CATP-5 operates in polyamine transport and is crucial for norspermidine-mediated suppression of RNA interference.

    PubMed

    Heinick, Alexander; Urban, Katja; Roth, Stefan; Spies, Danica; Nunes, Frank; Phanstiel, Otto; Liebau, Eva; Lüersen, Kai

    2010-01-01

    Physiological polyamines are required in various biological processes. In the current study, we used norspermidine, a structural analog of the natural polyamine spermidine, to investigate polyamine uptake in the model organism Caenorhabditis elegans. Norspermidine was found to have two remarkable effects: it is toxic for the nematode, without affecting its food, Escherichia coli; and it hampers RNA interference. By characterizing a norspermidine-resistant C. elegans mutant strain that has been isolated in a genetic screen, we demonstrate that both effects, as well as the uptake of a fluorescent polyamine-conjugate, depend on the transporter protein CATP-5, a novel P(5B)-type ATPase. To our knowledge, CATP-5 represents the first P(5)-type ATPase that is associated with the plasma membrane, being expressed in the apical membrane of intestinal cells and the excretory cell. Moreover, genetic interaction studies using C. elegans polyamine synthesis mutants indicate that CATP-5 has a function redundant to polyamine synthesis and link reduced polyamine levels to retarded postembryonic development, reduced brood size, shortened life span, and small body size. We suggest that CATP-5 represents a crucial component of the pharmacologically important polyamine transport system, the molecular nature of which has not been identified so far in metazoa.

  10. Inhibition of mTOR down-regulates scavenger receptor, class B, type I (SR-BI) expression, reduces endothelial cell migration and impairs nitric oxide production.

    PubMed

    Fruhwürth, Stefanie; Krieger, Sigurd; Winter, Katharina; Rosner, Margit; Mikula, Mario; Weichhart, Thomas; Bittman, Robert; Hengstschläger, Markus; Stangl, Herbert

    2014-07-01

    The mammalian target of rapamycin (mTOR) inhibiting drug rapamycin (Sirolimus) has severe side effects in patients including hyperlipidemia, an established risk factor for atherosclerosis. Recently, it was shown that rapamycin decreases hepatic LDL receptor (LDL-R) expression, which likely contributes to hypercholesterolemia. Scavenger receptor, class B, type I (SR-BI) is the major HDL receptor and consequently regulating HDL-cholesterol levels and the athero-protective effects of HDL. By using the mTOR inhibitor rapamycin, we show that SR-BI is down-regulated in human umbilical vein endothelial cells (HUVECs). This reduction of SR-BI protein as well as mRNA levels by about 50% did not alter HDL particle uptake or HDL-derived lipid transfer. However, rapamycin reduced HDL-induced activation of eNOS and stimulation of endothelial cell migration. The effects on cell migration could be counteracted by SR-BI overexpression, indicating that decreased SR-BI expression is in part responsible for the rapamycin-induced effects. We demonstrate that inhibition of mTOR leads to endothelial cell dysfunction and decreased SR-BI expression, which may contribute to atherogenesis during rapamycin treatment.

  11. Serum tumor markers.

    PubMed

    Perkins, Greg L; Slater, Evan D; Sanders, Georganne K; Prichard, John G

    2003-09-15

    Monoclonal antibodies are used to detect serum antigens associated with specific malignancies. These tumor markers are most useful for monitoring response to therapy and detecting early relapse. With the exception of prostate-specific antigen (PSA), tumor markers do not have sufficient sensitivity or specificity for use in screening. Cancer antigen (CA) 27.29 most frequently is used to follow response to therapy in patients with metastatic breast cancer. Carcinoembryonic antigen is used to detect relapse of colorectal cancer, and CA 19-9 may be helpful in establishing the nature of pancreatic masses. CA 125 is useful for evaluating pelvic masses in postmenopausal women, monitoring response to therapy in women with ovarian cancer, and detecting recurrence of this malignancy. Alpha-fetoprotein (AFP), a marker for hepatocellular carcinoma, sometimes is used to screen highly selected populations and to assess hepatic masses in patients at particular risk for developing hepatic malignancy. Testing for the beta subunit of human chorionic gonadotropin (beta-hCG) is an integral part of the diagnosis and management of gestational trophoblastic disease. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG also may be useful in evaluating potential origins of poorly differentiated metastatic cancer. PSA is used to screen for prostate cancer, detect recurrence of the malignancy, and evaluate specific syndromes of adenocarcinoma of unknown primary.

  12. Molecular classification of an elasmobranch angiotensin receptor: quantification of angiotensin receptor and natriuretic peptide receptor mRNAs in saltwater and freshwater populations of the Atlantic stingray.

    PubMed

    Evans, Andrew N; Henning, Toni; Gelsleichter, James; Nunez, B Scott

    2010-12-01

    Among the most conserved osmoregulatory hormone systems in vertebrates are the renin-angiotensin system (RAS) and the natriuretic peptides (NPs). We examined the RAS and NP system in the euryhaline Atlantic stingray, Dasyatis sabina (Lesueur). To determine the relative sensitivity of target organs to these hormonal systems, we isolated cDNA sequences encoding the D. sabina angiotensin receptor (AT) and natriuretic peptide type-B receptor (NPR-B). We then determined the tissue-specific expression of their mRNAs in saltwater D. sabina from local Texas waters and an isolated freshwater population in Lake Monroe, Florida. AT mRNA was most abundant in interrenal tissue from both populations. NPR-B mRNA was most abundant in rectal gland tissue from both populations, and also highly abundant in the kidney of saltwater D. sabina. This study is the first to report the sequence of an elasmobranch angiotensin receptor, and phylogenetic analysis indicates that the D. sabina receptor is more similar to AT(1) vs. AT(2) proteins. This classification is further supported by molecular analysis of AT(1) and AT(2) proteins demonstrating conservation of AT(1)-specific amino acid residues and motifs in D. sabina AT. Molecular classification of the elasmobranch angiotensin receptor as an AT(1)-like protein provides fundamental insight into the evolution of the vertebrate RAS.

  13. Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway.

    PubMed

    Yamamoto, Takashi; Wada, Atsuyuki; Tsutamoto, Takayoshi; Ohnishi, Masato; Horie, Minoru

    2004-11-01

    In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.

  14. Sensitivity and Specificity of Soluble Triggering Receptor Expressed on Myeloid Cells-1, Midregional Proatrial Natriuretic Peptide and Midregional Proadrenomedullin for Distinguishing Etiology and to Assess Severity in Community-Acquired Pneumonia

    PubMed Central

    Esposito, Susanna; Di Gangi, Maria; Cardinale, Fabio; Baraldi, Eugenio; Corsini, Ilaria; Da Dalt, Liviana; Tovo, Pier Angelo; Correra, Antonio; Villani, Alberto; Sacco, Oliviero; Tenero, Laura; Dones, Piera; Gambino, Monia; Zampiero, Alberto; Principi, Nicola

    2016-01-01

    Study Design This study aimed to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), midregional proatrial natriuretic peptide (MR-proANP) and midregional proadrenomedullin (MR-proADM) to distinguish bacterial from viral community-acquired pneumonia (CAP) and to identify severe cases in children hospitalized for radiologically confirmed CAP. Index test results were compared with those derived from routine diagnostic tests, i.e., white blood cell (WBC) counts, neutrophil percentages, and serum C-reactive protein (CRP) and procalcitonin (PCT) levels. Methods This prospective, multicenter study was carried out in the most important children’s hospitals (n = 11) in Italy and 433 otherwise healthy children hospitalized for radiologically confirmed CAP were enrolled. Among cases for whom etiology could be determined, CAP was ascribed to bacteria in 235 (54.3%) children and to one or more viruses in 111 (25.6%) children. A total of 312 (72.2%) children had severe disease. Results CRP and PCT had the best performances for both bacterial and viral CAP identification. The cut-off values with the highest combined sensitivity and specificity for the identification of bacterial and viral infections using CRP were ≥7.98 mg/L and ≤7.5 mg/L, respectively. When PCT was considered, the cut-off values with the highest combined sensitivity and specificity were ≥0.188 ng/mL for bacterial CAP and ≤0.07 ng/mL for viral CAP. For the identification of severe cases, the best results were obtained with evaluations of PCT and MR-proANP. However, in both cases, the biomarker cut-off with the highest combined sensitivity and specificity (≥0.093 ng/mL for PCT and ≥33.8 pmol/L for proANP) had a relatively good sensitivity (higher than 70%) but a limited specificity (of approximately 55%). Conclusions This study indicates that in children with CAP, sTREM-1, MR-proANP, and MR-proADM blood levels have poor abilities to differentiate

  15. Association of N-terminal pro-brain natriuretic peptide with contrast-induced acute kidney injury and long-term mortality in patients with heart failure and mid-range ejection fraction: An observation study.

    PubMed

    Wang, Kun; Li, Hua-Long; Chen, Li-Ling; Bei, Wei-Jie; Lin, Kai-Yang; Smyth, Brendan; Chen, Shi-Qun; Guo, Xiao-Sheng; Guo, Wei; Liu, Yuan-Hui; Chen, Peng-Yuan; Chen, Ji-Yan; Chen, Kai-Hong; Liu, Yong; Tan, Ning

    2017-03-01

    The potential value of N-terminal pro-brain natriuretic peptide (NT-proBNP) for contrast-induced acute kidney injury (CI-AKI) in patients with heart failure and mid-range ejection fraction (HFmrEF) is unclear. We investigated whether NT-proBNP is associated with CI-AKI and long-term mortality following elective cardiac catheterization in patients with HFmrEF.A total of 174 consecutive patients with HFmrEF undergoing elective coronary angiography or intervention were enrolled. The primary endpoint was the development of CI-AKI, defined as an absolute increase of ≥0.3 mg/dL or ≥ 50% from baseline serum creatinine with 48 hours after contrast medium exposure. Receiver-operating characteristic curve analysis was conducted, and Youden index was used to determine the best cutoff NT-proBNP value. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify the independent risk factors for CI-AKI and long-term mortality, respectively.The incidence of CI-AKI was 12.1%. Patients with CI-AKI had higher NT-proBNP values than those without (4373[1561.9-7470.5] vs 1303[625.2-2482.3], P = 0.003). Receiver-operating characteristic curve revealed that NT-proBNP was not significantly different from the Mehran risk score in predicting CI-AKI (area under the curve [AUC] = 0.723 vs 0.767, P = 0.516). The best cutoff NT-proBNP value for CI-AKI was 3299 pg/mL, with 70.6% sensitivity and 83.1% specificity. Multivariable analysis demonstrated that NT-proBNP ≥3299 pg/mL is significantly related to CI-AKI (odds ratio = 12.79; 95% confidence interval, 3.18-51.49; P < 0.001). Cox regression analysis showed that NT-proBNP ≥3299 pg/mL is associated with long-term mortality (adjusted hazard ratio = 11.91; 95%CI, 2.16-65.70; P = 0.004) during follow-up.In patients with HFmrEF, NT-proBNP ≥3299 pg/mL is associated with CI-AKI and long-term mortality following elective coronary angiography or

  16. Association of N-terminal pro-brain natriuretic peptide with contrast-induced acute kidney injury and long-term mortality in patients with heart failure and mid-range ejection fraction

    PubMed Central

    Wang, Kun; Li, Hua-long; Chen, Li-ling; Bei, Wei-jie; Lin, Kai-yang; Smyth, Brendan; Chen, Shi-qun; Guo, Xiao-sheng; Guo, Wei; Liu, Yuan-hui; Chen, Peng-yuan; Chen, Ji-yan; Chen, Kai-hong; Liu, Yong; Tan, Ning

    2017-01-01

    Abstract The potential value of N-terminal pro-brain natriuretic peptide (NT-proBNP) for contrast-induced acute kidney injury (CI-AKI) in patients with heart failure and mid-range ejection fraction (HFmrEF) is unclear. We investigated whether NT-proBNP is associated with CI-AKI and long-term mortality following elective cardiac catheterization in patients with HFmrEF. A total of 174 consecutive patients with HFmrEF undergoing elective coronary angiography or intervention were enrolled. The primary endpoint was the development of CI-AKI, defined as an absolute increase of ≥0.3 mg/dL or ≥ 50% from baseline serum creatinine with 48 hours after contrast medium exposure. Receiver-operating characteristic curve analysis was conducted, and Youden index was used to determine the best cutoff NT-proBNP value. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify the independent risk factors for CI-AKI and long-term mortality, respectively. The incidence of CI-AKI was 12.1%. Patients with CI-AKI had higher NT-proBNP values than those without (4373[1561.9–7470.5] vs 1303[625.2–2482.3], P = 0.003). Receiver-operating characteristic curve revealed that NT-proBNP was not significantly different from the Mehran risk score in predicting CI-AKI (area under the curve [AUC] = 0.723 vs 0.767, P = 0.516). The best cutoff NT-proBNP value for CI-AKI was 3299 pg/mL, with 70.6%