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Sample records for pro b-type natriuretic

  1. 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

  2. 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

  3. 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.

  4. 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

  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. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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/NT-pro

  1. 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

  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. 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

  5. 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.

  6. 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 ...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  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. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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).

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Pro-atrial natriuretic peptide and prediction of atrial fibrillation and stroke: The Malmö Preventive Project.

    PubMed

    Berntsson, John; Smith, J Gustav; Nilsson, Peter M; Hedblad, Bo; Melander, Olle; Engström, Gunnar

    2017-01-01

    Background The increasing prevalence of atrial fibrillation and novel therapeutic tools to prevent cardioembolic stroke has increased the need for risk markers. Objectives This study explored the relationship between the midregional sequence of pro-atrial natriuretic peptide (MR-proANP) levels with the risk of atrial fibrillation and stroke, and whether measurement of MR-proANP improves the prediction of these outcomes. Methods MR-proANP was measured in fasting blood samples of 5130 subjects (69% men, mean age 69.2 ± 6.2 years) without a history of atrial fibrillation or stroke from the general population. The incidence of atrial fibrillation and stroke was monitored over a median follow-up of 5.6 years. C-statistics and net reclassification improvement was used to assess the predictive ability of MR-proANP in addition to conventional risk factors. Results Log-normalized MR-proANP was significantly associated with the incidence of atrial fibrillation ( n = 362; hazard ratio (HR); 95% confidence interval (CI) per 1 standard deviation (SD) 2.05, 1.86-2.27) and stroke from all causes ( n = 195; HR 1.30; 95% CI 1.12-1.50). The HR for stroke events related to atrial fibrillation was 1.79 (95% CI 1.25-2.58) per 1 SD. MR-proANP significantly improved the prediction of atrial fibrillation when added to a risk score of conventional risk factors (C statistic 0.69 vs. 0.75), mainly by down-classifying subjects who did not develop atrial fibrillation. A smaller improvement in predictive ability was observed for stroke (C statistic 0.66 vs. 0.68). Conclusion High plasma levels of MR-proANP are associated with the incidence of atrial fibrillation and stroke in the middle-aged and elderly population. MR-proANP may be useful to identify individuals with an increased risk of atrial fibrillation.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease

    PubMed Central

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

    2015-01-01

    Objective Several papers have reported elevated plasma levels of natriuretic peptides in patients with a previous diagnosis of cancer. We have explored whether N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels predict a future diagnosis of cancer in patients with coronary artery disease (CAD). Methods We studied 699 patients with CAD free of cancer. At baseline, NT-proBNP, galectin-3, monocyte chemoattractant protein-1, soluble tumor necrosis factor-like weak inducer of apoptosis, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin I plasma levels were assessed. The primary outcome was new cancer diagnosis. The secondary outcome was cancer diagnosis, heart failure requiring hospitalization, or death. Results After 2.15±0.98 years of follow-up, 24 patients developed cancer. They were older (68.5 [61.5, 75.8] vs 60.0 [52.0, 72.0] years; p=0.011), had higher NT-proBNP (302.0 [134.8, 919.8] vs 165.5 [87.4, 407.5] pg/ml; p=0.040) and high-sensitivity C-reactive protein (3.27 [1.33, 5.94] vs 1.92 [0.83, 4.00] mg/L; p=0.030), and lower triglyceride (92.5 [70.5, 132.8] vs 112.0 [82.0, 157.0] mg/dl; p=0.044) plasma levels than those without cancer. NT-proBNP (Hazard Ratio [HR]=1.030; 95% Confidence Interval [CI]=1.008-1.053; p=0.007) and triglyceride levels (HR=0.987; 95%CI=0.975-0.998; p=0.024) were independent predictors of a new cancer diagnosis (multivariate Cox regression analysis). When patients in whom the suspicion of cancer appeared in the first one-hundred days after blood extraction were excluded, NT-proBNP was the only predictor of cancer (HR=1.061; 95%CI=1.034-1.088; p<0.001). NT-proBNP was an independent predictor of cancer, heart failure, or death (HR=1.038; 95%CI=1.023-1.052; p<0.001) along with age, and use of insulin and acenocumarol. Conclusions NT-proBNP is an independent predictor of malignancies in patients with CAD. New studies in large populations are needed to confirm these findings. PMID:26046344

  5. N-terminal pro-brain natriuretic peptide and cardiovascular or all-cause mortality in the general population: A meta-analysis

    PubMed Central

    Geng, Zhaohua; Huang, Lan; Song, Mingbao; Song, Yaoming

    2017-01-01

    The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the general population remains controversial. We conducted this meta-analysis to investigate the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population. PubMed and Embase databases were systematically searched from their inception to August 2016. Prospective observational studies that investigated the association between baseline NT-proBNP concentrations and cardiovascular or all-cause mortality in the general population were eligible. A summary of the hazard ratio (HR) and 95% confidence interval (CI) of mortality were calculated by the highest versus the lowest category of NT-proBNP concentrations. Eleven studies with a total of 25,715 individuals were included. Compared individuals in the highest with those in the lowest category of NT-proBNP, the pooled HR was 2.44 (95% CI 2.11–2.83) for all-cause mortality, 3.77 (95% CI 2.85–5.00) for cardiovascular mortality, and 2.35 (95% CI 1.45–3.82) for coronary heart disease mortality, respectively. Subgroup analyses indicated that the effects of NT-proBNP on the risk of cardiovascular mortality (RR 2.27) and all-cause mortality (RR 3.00) appeared to be slightly lower among men. Elevated NT-proBNP concentrations appeared to be independently associated with increased risk of cardiovascular and all-cause mortality in the general population. PMID:28134294

  6. Comparison of prognostic value of N-terminal pro-brain natriuretic peptide in septic and non-septic intensive care patients

    PubMed Central

    Ozcan, Ayse; Kaymak, Cetin; Basar, Hulya; Kotanoglu, Mustafa; Kose, Bektas

    2017-01-01

    Introduction The aim of this study is to compare the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in septic and non-septic intensive care patients. Material and methods Fifty consecutive patients admitted to the intensive care unit (ICU) were enrolled in either the septic or non-septic group according to the criteria in the International Sepsis Definitions Conference in 2001. Demographic and clinical data, procalcitonin and lactate levels at admission, and death within 28 days were registered. Five blood samples were collected from all patients for NT-proBNP measurements. Results Septic patients had higher APACHE II (19 (16.00–24.25) vs. 16 (13.00–18.25)), and SOFA (8 (5–10) vs. 6 (4–7)) scores (p <0.05). Procalcitonin levels were also higher in septic patients (3.33 (1.06–10.96) vs. 0.46 (0.26–1.01) ng/ml) and more patients required vasopressors in this group (9 (36%) vs. 2 (8%)) (p < 0.05). In the septic group, the correlation between mortality and the level of NT-proBNP was significant for each measurement, starting from the admission. In the non-septic group the correlation between mortality and the level of NT-proBNP was significant only at the 120th h. Conclusions We concluded that the level of NT-proBNP at admission is well correlated with 28-day mortality in septic ICU patients. However, single measurement of NT-proBNP levels in non-septic patients does not correlate with the 28-day mortality. Repeated measurements and an increasing trend of the NT-proBNP levels may show a correlation with mortality in non-septic intensive care patients. PMID:28261297

  7. 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

  8. 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).

  9. Increased Epicardial Fat Thickness Correlates with Aortic Stiffness and N-Terminal Pro-Brain Natriuretic Peptide Levels in Acute Ischemic Stroke Patients

    PubMed Central

    Unal, Yasemin; Basaran, Ozcan; Akin, Fatih; Emir, Gulser Karadaban; Kutlu, Gulnihal; Biteker, Murat

    2016-01-01

    Epicardial fat, a metabolically active tissue, has emerged as a risk factor and active player in metabolic and cardiovascular diseases. We investigated epicardial fat thickness in patients who had sustained an acute ischemic stroke, and we evaluated the relationship of epicardial fat thickness with other prognostic factors. We enrolled 61 consecutive patients (age, ≥18 yr) who had sustained a first acute ischemic stroke and had been admitted to our hospital within 24 hours of the onset of stroke symptoms. The control group comprised 82 consecutive sex- and age-matched patients free of past or current stroke who had been admitted to our cardiology clinics. Blood samples were taken for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at admission. Aortic stiffness indices and epicardial fat thickness were measured by means of transthoracic echocardiography within the first 48 hours. In comparison with the control group, the patients with acute ischemic stroke had significantly higher epicardial fat thickness (4.8 ± 0.9 vs 3.8 ± 0.7 mm; P <0.001), lower aortic distensibility (2.5 ± 0.8 vs 3.4 ± 0.9 cm2·dyn−1; P <0.001) and lower aortic strain (5.5% ± 1.9% vs 6.4% ± 1.8%; P=0.003). We found a significant association between epicardial fat thickness, NT-proBNP levels, and arterial dysfunction in patients who had sustained acute ischemic stroke. Increased epicardial fat thickness might be a novel risk factor and might enable evaluation of subclinical target-organ damage in these patients. PMID:27303237

  10. The proposed role of plasma NT pro-brain natriuretic peptide in assessing cardiac remodelling in hypertensive African subjects

    PubMed Central

    Ojji, Dike B; Opie, Lionel H; Lecour, Sandrine; Lacerda, Lydia; Sliwa, Karen; Adeyemi, Olusoji M

    2014-01-01

    Summary Aim Although plasma NT-proBNP differentiates hypertension (HT) with or without left ventricular hypertrophy (LVH) from hypertensive heart failure (HHF), most of the published data are based on studies in Western populations. Also, most previous studies did not consider left ventricular (LV) diastolic function and right ventricular (RV) function. We therefore examined the relation between NT-proBNP on LV and RV remodelling in an African hypertensive cohort. Methods Subjects were subdivided into three groups after echocardiography: hypertensives without LVH (HT) (n = 83); hypertensives with LVH (HT+LVH) (n = 50); and those with hypertensive heart failure (HHF) (n = 77). Results Subjects with HHF had significantly higher NT-proBNP levels compared to the HT+LVH group (p < 0.0002). NT-proBNP correlated positively with right atrial area, an indirect measure of RV function. Conclusions NT-proBNP is proposed as a useful biomarker in differentiating hypertension with or without LVH from hypertensive heart failure in black hypertensive subjects. PMID:25629540

  11. 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

  12. [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.

  13. 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

  14. 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

  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

    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% 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

  16. 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.

  17. 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

  18. 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.

  19. Long-term outcome of patients with triphasic mitral flow with a mid-diastolic L wave: prognostic role of left atrial volume and N-terminal pro-brain natriuretic peptide.

    PubMed

    Kim, Sung-Ai; Son, Jungwoo; Shim, Chi-Young; Choi, Eui-Young; Ha, Jong-Won

    2017-03-27

    A mid-diastolic L wave has been recognized as a marker of advanced left ventricular (LV) diastolic dysfunction. However, its prognostic implication is unclear. This study assessed long-term prognosis and independent predictors of adverse outcomes in patients with a mid-diastolic L wave. A total of 144 consecutive patients (mean age 63 ± 12 years, 88 female) with a mid-diastolic L wave of ≥0.2 m/s and in sinus rhythm were identified. Patients with significant valvular heart disease, low LV ejection fraction and arrhythmias were excluded. Subjects were followed up for cardiovascular (CV) mortality and hospitalization for heart failure (HF). During follow-up for a median of 44 months (1-76), CV deaths and hospitalization for HF occurred in 41 (28%) patients. In multivariate Cox analysis, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.001), log N-terminal pro-brain natriuretic peptide (NT-proBNP)(HR 3.81; 95% CI 1.78-8.15; p = 0.001), and left atrial volume index (HR 1.02; 95% CI 1.01-1.04; p = 0.019) were independent predictors of adverse outcomes in patients with a mid-diastolic L wave. In a stepwise model, NT-proBNP showed an incremental prognostic value for prediction of adverse outcomes when added to the clinical and echocardiographic parameters (Chi square from 30.1 to 41.1, p < 0.001). Patients with a mid-diastolic L wave and clinical, biochemical, and echocardiographic evidence of advanced diastolic dysfunction showed poor long-term clinical outcome.

  20. Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

    PubMed

    Claessens, Y-E; Schmidt, J; Batard, E; Grabar, S; Jegou, D; Hausfater, P; Kierzek, G; Guérin, S; Pourriat, J-L; Dhainaut, J-F; Ginsburg, C

    2010-06-01

    Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

  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. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein.

    PubMed

    Alqahtani, Mashael F; Smith, Craig M; Weiss, Scott L; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11). MMP-9/TIMP-1 ratios were

  3. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein

    PubMed Central

    Alqahtani, Mashael F.; Smith, Craig M.; Weiss, Scott L.; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S.

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004–0.174, 13), day 2 (0.020, 0.002–0.109, 10), and day 3 (0.018, 0.003–0.058, 23) compared with febrile (0.705, 0.187–1.778, 22) and healthy (0.7, 0.4–1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2–54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3–20.6, 11). MMP-9/TIMP-1 ratios

  4. [N-terminal pro-brain natriuretic peptide levels and diastolic dysfunction in patients with early rheumatoid arthritis before the administration of disease-modifying antirheumatic drugs].

    PubMed

    Kirillova, I G; Novikova, D S; Popkova, T V; Aleksandrova, E N; Novikov, A A; Gorbunova, Yu N; Markelova, E I; Korsakova, Yu O; Glukhova, S I; Volkov, A V; Luchikhina, E L; Demidova, N V; Kasumova, K A; Vladimirov, S A; Kanonirova, M A; Lukina, G L; Karateev, D E; Nasonov, E L

    2016-01-01

    Резюме Цель исследования. Определить уровень N-концевого натрийуретического пептида (NT-proBNP) у больных ранним ревматоидным артритом (РА) до назначения базисных противовоспалительных препаратов (БПВП), сопоставить уровень NT-proBNP с традиционными факторами риска (ТФР), сердечно-сосудистыми заболеваниями (ССЗ), маркерами воспаления и диастолической дисфункцией (ДД) миокарда левого желудочка (ЛЖ). Материалы и методы. В исследование включили 74 пациента с достоверным диагнозом РА (критерии ACR/EULAR, 2010), 56 (74%) женщин, медиана (Ме) возраста 54 года, длительности заболевания 7 мес; серопозитивные по ревматоидному фактору класса IgM (87%) и/или антителам к циклическому цитруллинированному пептиду (100%) без опыта приема БПВП и глюкокортикостероидов. Оценка ТФР развития ССЗ, атеросклероза сонных артерий (АСА) по данным дуплексного сканирования и эхокардиография проведены у всех пациентов с ранним РА до начала терапии. В качестве критерия ДДЛЖ использовали соотношение Е/А. Результаты. Концентрация NT-proBNP у больных ранним РА оказалась выше, чем в группе контроля (р<0,0001). У 36 (49%) больных РА уровень NT-proBNP

  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. [Value of N-terminal pro brain natriuretic peptide in predicting acute kidney injury in patients with acute decompensated chronic heart failure].

    PubMed

    Menzorov, M V; Shutov, A M; Midlenko, V I; Larionova, N V; Morozova, I V; Akulova, O V

    2017-01-01

    Цель исследования. Изучить прогностическое значение N-концевого предшественника мозгового натрийуретического пептида (NT-proBNP) сыворотки крови в развитии острого повреждения почек (ОПП) у больных с острой декомпенсацией хронической сердечной недостаточности (ОДХСН). Материалы и методы. Обследовали 83 больных с ОДХСН — 55 (66%) мужчин и 28 (34%) женщин, средний возраст составил 65±11 лет. ОПП диагностировали и классифицировали согласно Рекомендациям KDIGO (2012). Чтобы исключить индуцированное контрастным веществом ОПП, в исследование включили только пациентов, которым во время госпитализации и за 7 дней до нее не вводились рентгеноконтрастные препараты. У всех пациентов при поступлении в стационар определяли концентрацию NT-proBNP в сыворотке крови иммуноферментным методом. Результаты. ОПП диагностировано у 18 (22%) больных, причем у 13 (16%) I стадию, 4 (5%) II стадию, 1 (1%) III стадию ОПП. Концентрация NT-proBNP в сыворотке крови была достоверно выше у больных с ОПП по сравнению с остальными пациентами — 1512,1 (981,0; 2246,2) и 861,8 (499,0; 1383,6) пг/мл (p=0,008). Установлено, что концентрация NT-proBNP более 942 пг/мл ассоциирована со з

  7. 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.

  8. 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.

  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. 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.

  11. 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.

  12. 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

  13. Association of NT-proBNP and interleukin-17 levels with heart failure in elderly patients.

    PubMed

    Li, X F; Pan, D; Zhang, W L; Zhou, J; Liang, J J

    2016-05-13

    Pro-B-type natriuretic peptide (NT-proBNP) and interleukin-17 (IL-17) are involved in the pathophysiological processes of heart failure; however, the exact role of IL-17 is not clear. We explored the relationship between IL-17 and NT-proBNP, as a clinical parameter, in heart failure. The whole blood IL-17 and NT-proBNP levels and the readmission rates in 70 patients with chronic heart failure class III or IV according to the New York Heart Association and 35 patients with normal heart function (control group) were measured and compared. The left ventricle ejection fractions (LVEFs) and NT-proBNP and IL-17 levels in cardiac functional class III (40.38 ± 4.76%, 7780 ± 6393 pg/mL, 8.65 ± 3.05 pg/mL, respectively) and class IV (31.59 ± 4.31%, 13,704 ± 10,945, 21.10 ± 10.60 pg/mL, respectively) were higher than those in the control group (61.27 ± 5.66%, 420 ± 256 pg/mL, 3.53 ± 2.05 pg/mL, respectively). Compared to the cardiac functional class IV, class III showed significantly higher values for LVEF and NT-proBNP and IL-17 levels (P < 0.05). The readmission rates of the patients in cardiac functional class III at 3 and 6 months (15.7 and 34.4%, respectively) and cardiac functional class IV at 3 and 6 months (39.5 and 76.3%, respectively) were significantly higher than those in the control group (0 and 5.7%, respectively) (P < 0.05). The NT-proBNP and IL-17 levels increased as the heart function worsened. NT-proBNP and IL-17 may play essential roles in the process of heart failure.

  14. 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

  15. Prognostic utility of right ventricular systolic functions assessed by tissue doppler imaging in dilated cardiomyopathy and its correlation with plasma NT-pro-BNP levels.

    PubMed

    Tigen, Kursat; Karaahmet, Tansu; Cevik, Cihan; Gurel, Emre; Pala, Selcuk; Mutlu, Bulent; Basaran, Yelda

    2009-01-01

    The authors invesitgated the impact of right ventricular systolic function measured by tissue Doppler imaging on clinical end points and its correlation with plasma NT-pro-BNP levels in 75 patients with nonischemic dilated cardiomyopathy. Echocardiographic peak systolic velocities of tricuspid lateral annulus by tissue Doppler imaging and plasma pro-B-type natriuretic peptide (NT-pro-BNP) levels were measured. Forty patients had clinical end points in 29+/-16 months. They were found to have higher plasma NT-pro-BNP levels and lower tricuspid lateral annulus and interventricular septum tissue Doppler peak systolic velocities than patients without clinical end points. Cut-off level of plasma NT-pro-BNP levels for predicting clinical end points was 1700 pg/mL (sensitivity and specificity, 82% and 75%, respectively). Cut-off level of tricuspid lateral annulus tissue Doppler peak systolic velocities for predicting clinical end points was 6.25 cm/sec (sensitivity and specificity, 80% and 57%, respectively). In conclusion, plasma NT-pro-BNP levels and tissue Doppler-derived right ventricular systolic functional parameters are helpful in determining prognosis in dilated cardiomyopathy.

  16. New insight into the role of NT-proBNP in alcoholic liver cirrhosis as a noninvasive marker of esophageal varices

    PubMed Central

    Ljubičić, Neven; Gomerčić, Marija; Zekanović, Dražen; Bodrožić-, Tomislava; Džakić; Đuzel, Ana

    2012-01-01

    Aim To investigate the association between plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and formation of esophageal varices. Methods Thirty-five patients with alcoholic cirrhosis were divided into three groups according to the Child-Pugh classification: grade A (n = 11, 32%), B (n = 12, 34%), and C (n = 12, 34%). System hemodynamic parameters were measured using sphygmomanometry, electrocardiography, and echocardiography. NT-proBNP was analyzed by using an electrochemiluminiscence sandwich immunoassay. Results The presence of esophageal varices was associated with a higher serum NT-proBNP level, with a cut-off value of >101 pg/mL (sensitivity, 87.60% and specificity, 72.73%; P < 0.001). Conclusions NT-proBNP was found to be a marker of the presence of esophageal varices, but not a marker of progression of liver cirrhosis. In cirrhotic patients, NT-proBNP value >101 pg/mL was shown to be a valuable noninvasive parameter in predicting the presence of varices. PMID:22911531

  17. [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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension.

    PubMed

    Wang, Tzung-Dau; Tan, Ru-San; Lee, Hae-Young; Ihm, Sang-Hyun; Rhee, Moo-Yong; Tomlinson, Brian; Pal, Parasar; Yang, Fan; Hirschhorn, Elizabeth; Prescott, Margaret F; Hinder, Markus; Langenickel, Thomas H

    2017-01-01

    Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: -20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH.

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. 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...

  8. NT-proBNP in Children With Left to Right Shunt and Dilated Cardiomyopathy

    PubMed Central

    Koura, Hala Mahmoud; Abdalla, Neamat M.; Hamed Ibrahim, Mona; Abo Hashish, Maha M. A.; Zaki, Sherif Mohamed

    2016-01-01

    Background B-type natriuretic peptide (BNP) levels are elevated in children with congenital heart disease involving a left-to-right shunt (LRS) and are also raised in dilated cardiomyopathy (DCM). As far as we know, there are few reports in the literature comparing the change of the NT-proBNP in LRS and DCM especially in the pediatric age group. Objectives The aim of the study was to compare the changes of the NT-proBNP in pediatric patients with LRS and DCM. Correlation between the levels of NT-proBNP and the echocardiographic parameters in both groups was determined. Patients and Methods A total of 30 children (13 males and 17 females) participated in the study. There were 11/30 (36.7%) DCM and 19/30 (63.3%) LRS. The control group consisted of 44 healthy infants and children. Manifestations of heart failure (decompensation) were recorded. The NT-pro BNP levels were measured. The following Echo parameters were assessed: systolic function (ejection fraction and fraction shortening), pulmonary to systemic flow (Qp/Qs) in LRS, pulmonary flow and pulmonary artery pressure (SPAP) and LV diastolic function (E-wave, A-wave, E/A ratio and deceleration time). Results Clinically 17/30 (56.7%) (11 of the LRS and 5 of the DCM) were decompensated. Significant shunt was present in 15/19 (78.9%) in LRS. Systolic dysfunction was presented in 5/30 (16.7%) cases (4 patients were DCM and one case was LRS). Two types of diastolic dysfunction, impaired relaxation in 5/22 (22.7%) patients and restrictive-like filling pattern in 5/16 (31.2 %) were observed. The NT-Pro BNP level was significantly elevated 11 and 16 times in the LRS and DCM groups respectively. Negative significant correlations were observed between the levels of NT-ProBNP and the following echo variables; EDD, LAD, E wave and E/A ratio in the LRS patients. Positive significant correlations were observed between the levels of NT-ProBNP and the following echo variables; PAP and QP/QS in the LRS. Both the PAP and QP/QS were

  9. 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

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. [BNP or NT-proBNP: "that is the question"].

    PubMed

    Lebrun, C; Neuder, Y; Pison, C; Chouri, N; Barnoud, D; Belle, L; Beaune, G

    2007-01-01

    Blood measurements of BNP and NT-proBNP, its catabolite, improve diagnosis for patients admitted to emergency departments with dyspnoea. In this paper, we have compared the BNP to the NT-proBNP for 119 dyspnoeic patients using at random clear clinical status. Among the test group of 119 patients, 57 showed coherent biological results for the 2 markers. These results confirm the final clinical diagnosis. Nine patients with congestive heart failure had abnormally low BNP and NT-proBNP rates. Six of these patients experienced long delays (longer than 48 hours and less than 72 hours) between their admission in emergency and the biological measurement of the natriuretic biomarkers. Three of the other patients could be not only flash OAP cases with a fast growth and a fast normalisation of BNP but also could have existing genetical factors. These genetical factors leading to high variability in BNP synthesis are not related to physiological or cardiac factors. 43 patients showed a mismatch between BNP and NT-proBNP. BNP appeared to be unstable in vitro. The lack of stability in whole blood or plasma samples is increased by sampling in a glass EDTA collection tube and too long delays in transferring the samples from the emergency area and the laboratory in a big hospital. Ten patients showed a mismatch with abnormally high NT-proBNP or false positive results. Among these 10 patients, 5 had renal dysfunction with a high level of creatinine concentration. It is clear that all Diagnostics Manufacturers should now propose different cut-off for natriuretic peptides tests according to the degree of patients' renal impairment.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Development and Evaluation of Up-Converting Phosphor Technology-Based Lateral Flow Assay for Quantitative Detection of NT-proBNP in Blood

    PubMed Central

    Hao, Qingfang; Zou, Deyong; Zhang, Xiaoli; Zhang, Liping; Li, Hongmei; Qiao, Yong; Zhao, Huansheng; Zhou, Lei

    2017-01-01

    A newly assay, up-converting phosphor technology-based lateral flow (UPT-LF) assay, was developed for rapid and quantitative detection of N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP), one of the most important serum molecular maker of heat failure, in plasma samples as a point of care testing (POCT) method for diagnosis of acute heart failure. Human plasma from 197 patients with acute heart failure and 200 healthy controls was assessed using the UPT-LF assay, in a comparison with a Roche Elecsys assay. The limit of detection of the UPT-LF assay, with a coefficient of variation (CV) of less than 15%, was 116 ng/L, which is lower than the clinical diagnosis cutoff (150 ng/mL). The linear range was 50–35,000 ng/L. The CVs were less than 10% for both UPT-LF and Roche Elecsys assays for plasma samples under different storages, demonstrating the good stability and reproducibility. There are certain linear correlations between the results of UPT-LF and Roche Elecsys assay for EDTA-K2 and heparin-anticoagulated plasma, as well as for serum samples. For UPT-LF assay, there is a significant correlation between the values derived from analysis of EDTA-K2 and heparin-anticoagulated plasma samples (R = 0.995). No statistically significant difference was found between serum and plasma samples for UPT-LF assay. Our results demonstrate that NT-proBNP levels in healthy adults are elevated with age and had a relationship with sex, and with the age increase the NT-proBNP levels of females are significantly higher than those of males (p<0.01). The UPT-LF assay has a high reproducibility, stability, sensitivity, specificity, and is consistent with Roche Elecsys assay, and therefore it could be used as a POCT method for the quantitative detection of NT-proBNP in blood for clinical diagnosis and research of acute heart failure. PMID:28151978

  7. Brain natriuretic peptide predicts forced vital capacity of the lungs, oxygen pulse and peak oxygen consumption in physiological condition.

    PubMed

    Popovic, Dejana; Ostojic, Miodrag C; Popovic, Bojana; Petrovic, Milan; Vujisic-Tesic, Bosiljka; Kocijancic, Aleksandar; Banovic, Marko; Arandjelovic, Aleksandra; Stojiljkovic, Stanimir; Markovic, Vidan; Damjanovic, Svetozar S

    2013-05-01

    Brain natriuretic peptide (NT-pro-BNP) is used as marker of cardiac and pulmonary diseases. However, the predictive value of circulating NT-pro-BNP for cardiac and pulmonary performance is unclear in physiological conditions. Standard echocardiography, tissue Doppler and forced spirometry at rest were used to assess cardiac parameters and forced vital capacity (FVC) in two groups of athletes (16 elite male wrestlers (W), 21 water polo player (WP)), as different stress adaptation models, and 20 sedentary subjects (C) matched for age. Cardiopulmonary test on treadmill (CPET), as acute stress model, was used to measure peak oxygen consumption (peak VO2), maximal heart rate (HRmax) and peak oxygen pulse (peak VO2/HR). NT-pro-BNP was measured by immunoassey sandwich technique 10min before the test - at rest, at the beginning of the test, at maximal effort, at third minute of recovery. FVC was higher in athletes and the highest in W (WP 5.60±0.29 l; W 6.57±1.00 l; C 5.41±0.29 l; p<0.01). Peak VO2 and peak VO2/HR were higher in athletes and the highest in WP. HRmax was not different among groups. In all groups, NT-pro-BNP decreased from rest to the beginning phase, increased in maximal effort and stayed unchanged in recovery. NT-pro-BNP was higher in C than W in all phases; WP had similar values as W and C. On multiple regression analysis, in all three groups together, ΔNT-pro-BNP from rest to the beginning phase independently predicted both peak VO2 and peak VO2/HR (r=0.38, 0.35; B=37.40, 0.19; p=0.007, 0.000, respectively). NT-pro-BNP at rest predicted HRmax (r=-0.32, B=-0.22, p=0.02). Maximal NT-pro-BNP predicted FVC (r=-0.22, B=-0.07, p=0.02). These results show noticeable predictive value of NT-pro-BNP for both cardiac and pulmonary performance in physiological conditions suggesting that NT-pro-BNP could be a common regulatory factor coordinating adaptation of heart and lungs to stress condition.

  8. 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

  9. 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.

  10. Cystatin C and NT-proBNP as prognostic biomarkers in Fabry disease.

    PubMed

    Torralba-Cabeza, Miguel-Ángel; Olivera, Susana; Hughes, Derralynn A; Pastores, Gregory M; Mateo, Ramón Nuviala; Pérez-Calvo, Juan-Ignacio

    2011-11-01

    Fabry disease (FD) is a lysosomal storage disorder caused by mutations in the α-galactosidase A gene. It is characterized by the deposition of the incompletely metabolized substrate globotriaosylceramide in several cell types and multisystem involvement. Major morbidity results from renal, cardiac and cerebrovascular pathology, mediated by endothelial dysfunction. We examined the potential utility of Cystatin C and natriuretic peptides as biomarkers in FD, and evaluated serum levels in 89 FD patients with varying degrees of disease severity. The results revealed that as a prognostic marker, Cystatin C is a good and cost effective indicator of early renal dysfunction and/or heart failure in FD. It is also more useful than serum creatinine in detecting mild renal damage and small decreases in glomerular filtration. In addition, the natriuretic peptide NT-proBNP, was elevated in patients with FD and cardiac involvement, and found to be an adequate detection marker, not only of cardiac involvement, but also of diastolic dysfunction.

  11. 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.

  12. B‐type Natriuretic Peptides for the Prediction of Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study

    PubMed Central

    Mishra, Rakesh K.; Beatty, Alexis L.; Jaganath, Rajesh; Regan, Mathilda; Wu, Alan H.B.; Whooley, Mary A.

    2014-01-01

    Background Brain‐type natriuretic peptide (BNP) and the amino‐terminal fragment of its prohormone (NT‐proBNP) are known predictors of cardiovascular outcomes in patients with coronary heart disease; however, the relative prognostic value of these 2 biomarkers for secondary events remains unclear. Methods and Results In 983 participants with stable coronary heart disease, we evaluated the association of BNP and NT‐proBNP with time to hospitalization for heart failure, nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and combined major adverse cardiovascular events (MACE). During an average follow‐up of 6.5±3.3 years, both BNP and NT‐proBNP were associated with increased risk of MACE in a multivariable‐adjusted model (hazard ratio per standard deviation of log BNP: 1.58; 95% CI: 1.32 to 1.89; hazard ratio per standard deviation of log NT‐proBNP: 1.84; 95% CI: 1.52 to 2.24). When added to traditional risk factors, NT‐proBNP predicted MACE better than BNP (C statistic: 0.76 versus 0.72, P<0.001). Similarly, the addition of NT‐proBNP resulted in a greater net reclassification improvement for predicting MACE than the addition of BNP (65% for NT‐proBNP, 56% for BNP). Conclusions Both BNP and NT‐proBNP were significant predictors of MACE in stable coronary heart disease; however, NT‐proBNP was superior to BNP for net risk reclassification for MACE. PMID:25053234

  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. 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...

  15. 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...

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. Higher level of NT-proCNP in cerebrospinal fluid of patients with meningitis.

    PubMed

    Tomasiuk, Ryszard; Lipowski, Dariusz; Szlufik, Stanislaw; Peplinska, Krystyna; Mikaszewska-Sokolewicz, Malgorzata

    2016-02-12

    Aminoterminal pro-C type natriuretic peptide (NT-proCNP) as an active form of CNP, has been recently proven to be a potential marker of sepsis and to be linked to inflammatory diseases. So far, there are no studies describing the level of NT-proCNP in meningitis. The purpose of this study was to evaluate the diagnostic value of NT-proCNP in cerebrospinal fluid (CSF) in patients with meningitis and to compare it with the serum level of CRP and procalcitonin (PCT) in this group of patients. The results were compared to serum levels of CRP, PCT and CSF levels of cytosis, protein and lactate. NT-proCNP levels were statistically significant between the control group and the meningitis groups (p=0.02; R=0.3). We also noted a correlation between the level of NT-proCNP in the CSF of all of the study groups (controls and meningitis patients) and the CSF levels of cytosis (p<0.5; R=0.43), protein (p<0.05; R=0.39) and lactate (p<0.05; R=0.34), and also the serum level of CRP (p<0.05; R=0.30), but not serum PCT (p>0.05; R=0.11). These results suggest that NT-proCNP could be a potential marker of meningitis, but it cannot be used to distinguish between the types of meningitis.

  2. 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

  3. 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.

  4. [Diagnostic accuracy of NT-proBNP compared with electrocardiography in detecting left ventricular hypertrophy of hypertensive origin].

    PubMed

    Andrade, Helder; Morillas, Pedro; Castillo, Jesús; Roldán, Julián; Mateo, Irene; Agudo, Pilar; Quiles, Juan; Bertomeu-Martínez, Vicente

    2011-10-01

    Electrocardiography (ECG) is the most widely used method for diagnosing left ventricular hypertrophy (LVH) in hypertensive patients. We assessed the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) determination compared with ECG for detecting LVH in 336 consecutive hypertensive patients with preserved systolic function. We found a significant correlation between NT-proBNP levels and left ventricular mass adjusted for body surface area (r=.41; P<.001). The area under the receiver operating characteristic curve was 0.75 (95% CI, 0.7-0.8). A cut-off of 74.2 pg/mL had a greater sensitivity than ECG (76.6% vs 25.5%; P<.001) and a higher negative predictive value (87.8% vs 76.6%; P<.001) in the identification of LVH. NT-proBNP determination may be a useful tool for LVH screening in hypertensive patients.

  5. 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.

  6. 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

  7. 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).

  8. 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.

  9. 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.

  10. ProMat

    SciTech Connect

    2008-06-12

    ProMAT is a software tool for statistically analyzing data from enzyme-linked immunosorbent assay microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Fibrinopeptide A binds Gly-Pro-Arg-Pro.

    PubMed Central

    Root-Bernstein, R S; Westall, F C

    1984-01-01

    The tetrapeptide Gly-Pro-Arg-Pro inhibits fibrinogen aggregation, probably by binding to the same sites used during initiation of fibrin formation. The Gly-Pro-Arg-Pro binding sites have not yet been identified. However, their possible sequence and locations have been predicted on the basis of the amino acid pairing hypothesis. One of these predicted sites is on fibrinopeptide A. We report here that nuclear magnetic resonance studies indicate that Gly-Pro-Arg-Pro binds to fibrinopeptide A with a binding constant, K, of ca. 10(4) per mol. We also report results of 19 related peptide combinations used as controls. PMID:6589598

  4. TOXIRAE PRO PID

    EPA Science Inventory

    The ToxiRAE Pro PID measures total volatile organic compounds (VOCs) using a photoionization detector (PID). This sensor can be programmed to measure concentrations of a specified compound automatically and has a real time reading of VOC concentrations in parts per million (ppm) ...

  5. New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure

    PubMed Central

    Valenzuela-Méndez, Blanca; Rodríguez-Gutiérrez, Juan Francisco; Estella-García, Ángel; González-García, María Ángela

    2016-01-01

    Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator. It has been described high levels in septic patients, interacting directly with the relaxation of vascular tone, triggering hypotension of these patients. It is also found high levels in other diseases such as hypertension, heart failure, respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels and clearance marker to the 2nd–5th days of admission help to determine the poor performance and the risk of mortality in patients with severe sepsis admitted to the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C-reactive protein (CRP) levels to determine an unfavorable outcome and the risk of mortality in patients with sepsis admitted to the ICU. It has also proved useful in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM levels are independent of the germ conversely it is related to the magnitude of organ failure and therefore severity. We consider advisable incorporating the MR-proADM the panel of biomarkers necessary for the diagnosis and treatment of critically ill patients admitted to the ICU with severe sepsis. The combined PCT and MR-proADM levels could represent a valid tool in the clinical practice to timely identify patients with bacterial infections and guide the diagnosis and treatment of sepsis and septic shock. PMID

  6. Circulating N-terminal brain natriuretic peptide and cardiac function in response to acute systemic hypoxia in healthy humans

    PubMed Central

    2014-01-01

    Background As it remains unclear whether hypoxia of cardiomyocytes could trigger the release of brain natriuretic peptide (BNP) in humans, we investigated whether breathing normobaric hypoxic gas mixture increases the circulating NT-proBNP in healthy male subjects. Methods Ten healthy young men (age 29 ± 5 yrs, BMI 24.7 ± 2.8 kg/m2) breathed normobaric hypoxic gas mixture (11% O2/89% N2) for one hour. Venous blood samples were obtained immediately before, during, and 2 and 24 hours after hypoxic exposure. Cardiac function and flow velocity profile in the middle left anterior descending coronary artery (LAD) were measured by Doppler echocardiography. Results Arterial oxygen saturation decreased steadily from baseline value of 99 ± 1% after the initiation hypoxia challenge and reached steady-state level of 73 ± 6% within 20–30 minutes. Cardiac output increased from 6.0 ± 1.2 to 8.1 ± 1.6 L/min and ejection fraction from 67 ± 4% to 75 ± 6% (both p < 0.001). Peak diastolic flow velocity in the LAD increased from 0.16 ± 0.04 to 0.28 ± 0.07 m/s, while its diameter remained unchanged. In the whole study group, NT-proBNP was similar to baseline (60 ± 32 pmol/ml) at all time points. However, at 24 h, concentration of NT-proBNP was higher (34 ± 18%) in five subjects and lower (17 ± 17%), p = 0.002 between the groups) in five subjects than at baseline. Conclusion In conclusion, there is no consistent increase in circulating NT-proBNP in response to breathing severely hypoxic normobaric gas mixture in healthy humans, a possible reason being that the oxygen flux to cardiac myocytes does not decrease because of increased coronary blood flow. However, the divergent individual responses as well as responses in different cardiac diseases warrant further investigations. PMID:24989366

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Effects of immobilizations stress with or without water immersion on the expression of atrial natriuretic peptide in the hearts of two rat strains

    PubMed Central

    Slavikova, Jana; Mistrova, Eliska; Klenerova, Vera; Kruzliak, Peter; Caprnda, Martin; Hynie, Sixtus; Sida, Pavel; Dvorakova, Magdalena Chottova

    2016-01-01

    Atrial natriuretic peptide (ANP) is produced and released by mammalian cardiomyocytes and induces natriuresis, diuresis, and lowering of blood pressure. The present study examined localization of ANP and a possible role of the hypothalamic-pituitary-adrenal axis (HPA) activity on the expression of proANP gene in the heart. The Sprague Dawley (SD) and Lewis (LE) rat strains were used. The animals were exposed to the two types of stress: immobilization and immobilization combined with water immersion for 1 hour. Localization of ANP was detected by immunohistochemistry and expression of the proANP mRNA by real-time qPCR in all heart compartments of control and stressed animals after 1 and 3 hours after stress termination (IS1, IS3, ICS1, and ICS3). Relatively high density of ANP-immunoreactivity was observed in both atria of both rat strains. In control rats of both strains, the expression of the proANP mRNA was higher in the atria than in ventricles. In SD rats with the intact HPA axis, an upregulation of ANP gene expression was observed in the right atrium after IS1, in both atria and the left ventricle after IS3 and in the left atrium and the left ventricle after ICS3. In LE rats with a blunted reactivity of the HPA axis, no increase or even a downregulation of the gene expression was observed. Thus, acute stress-induced increase in the expression of the proANP gene is related to the activity of the HPA axis. It may have relevance to ANP-induced protection of the heart. PMID:27508036

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Total plasma proANP increases with atrial dilatation in horses.

    PubMed

    Van Der Vekens, N; Hunter, I; Timm, A; Decloedt, A; De Clercq, D; Deprez, P; Goetze, J P; van Loon, G

    2015-12-19

    Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total proANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration was significantly (P<0.001) higher in horses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; P<0.001) or horses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation was calculated. Sample storage at -80°C did not differ from sample storage at -20°C. The measurement of total proANP in plasma detects atrial dilatation in horses and may be useful for clinical evaluation in equine medicine.

  9. Pro-Active Behavior Management.

    ERIC Educational Resources Information Center

    McCormack, James E., Jr.

    The paper outlines the basic tactics in pro-active behavior management, a behavior modification approach for use with severely handicapped students which reorders the staff/student relationship by focusing on positive interaction. Pro-active behavior management is noted to involve interruption of established behavior chains, environmental…

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Tempus Pro Patient Monitoring System

    DTIC Science & Technology

    2015-04-03

    AFRL-SA-WP-TR-2015-0006 Tempus Pro Patient Monitoring System Nigel D. Pritchard 3 April 2015 Final Report... System 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Nigel D. Pritchard 5e. TASK NUMBER...subsequent demonstration of the Tempus Pro patient monitoring system to include the AF3899L critical care patient movement record. 15. SUBJECT TERMS

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

    PubMed

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

    2016-02-01

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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

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

    PubMed Central

    Martín-Reyes, Roberto; Franco-Peláez, Juan Antonio; Lorenzo, Óscar; González-Casaus, María Luisa; Pello, Ana María; Aceña, Álvaro; Carda, Rocío; Martín-Ventura, José Luis; Blanco-Colio, Luis; Martín-Mariscal, María Luisa; Martínez-Milla, Juan; Villa-Bellosta, Ricardo; Piñero, Antonio; Navarro, Felipe; Egido, Jesús; Tuñón, José

    2016-01-01

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

  6. 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

  7. 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

  8. Serum levels of NT- pro ANP, BNP, NT-pro BNP and function of the left atrium in patients with heart failure and preserved ejection fraction after myocardial infarction

    NASA Astrophysics Data System (ADS)

    Shurupov, V.; Suslova, T.; Ryabov, V.

    2015-11-01

    The objective of our study was to evaluate the levels of natriuretic peptides in patients (pts) with heart failure with preserved ejection fraction (HFpEF) in 12 month after ST elevation myocardial infarction (STEMI) with a focus on the function of left atrium (LA) and left ventricular (LV) filling pressure. 55 pts were included in the study. 6-minute walk test was performed. Echo exam was performed by the diagnostic system VIVID 7. BNP in whole blood was determined using the Triage ® Meter BNP test. The serum levels of NT-pro BNP, NT-pro ANP («Biomedica», Austria) were determined in blood samples by enzyme-linked immune-sorbent assay (ELISA). LA volume index were differences (16.03±3.39 ml/m2; 25.36±8.26 ml/m2; 29.41±9.46 ml/m2 accordingly I, II, III class) depending on severity of HF. Well as E/E' ratio were differences (7.5±1.4; 9.8±5.1; 13.5±7.6 accordingly I, II, III class) depending on severity of HF. The LA volume index correlated with levels of NT-pro ANP (R=0.29; p=0.04), levels of NT-pro BNP (R=0.37; p=0.01), levels of BNP (R=0.51; p=0.0001). The LV filling pressure correlated with levels of NT-pro ANP (R=0.45; p=0.002), levels of NT-pro BNP (R=0.49; p=0.001), levels of BNP (R=0.37; p=0.01).

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. [Pro Familia statistics for 1974].

    PubMed

    1975-09-01

    Statistics for 1974 for the West German family planning organization Pro Familia are reported. 56 offices are now operating, and 23,726 clients were seen. Men were seen more frequently than previously. 10,000 telephone calls were also handled. 16-25 year olds were increasingly represented in the clientele, as were unmarried persons of all ages. 1,242 patients were referred to physicians or clinics for clinical diagnosis.

  16. Association between vitamin D levels and left ventricular function and NT-proBNP levels among thalassemia major children with iron overload

    PubMed Central

    Ambarwati, Leny; Rahayuningsih, Sri Endah; Setiabudiawan, Budi

    2016-01-01

    Background: Heart disease is the major cause of death in thalassemia patients. Repeated blood transfusions and hemolysis cause iron overload and also disrupts the hydroxylation and synthesis of vitamin D, causing vitamin D deficiency. Vitamin D deficiency is associated with cardiac dysfunction. Objective: The purpose of this study was to determine the association between vitamin D levels and left ventricular function and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in thalassemia major children with iron overload. Patients and Methods: A cross-sectional study was conducted in March-April 2015 in the thalassemia clinic, Department of Child Health, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Thirty-four children with thalassemia were enrolled consecutively. Serum vitamin D and NT-proBNP levels were measured with electrochemiluminescence (ECLIA) method and echocardiography was performed to assess ventricular function. Results: Significant correlations were found between vitamin D levels and left ventricular ejection fraction (LVEF) (r = 0.399, P = 0.019) and fractional shortening (FS) (r = 0.394, P = 0.021). There was also significant correlation between vitamin D and NT-proBNP levels (r = -0.444, P = 0.008). Chi-square analysis also showed a relationship between vitamin D and NT-proBNP (P = 0.019) levels. There was a difference in NT-proBNP levels among thalassemia major children with iron overload (P = 0.020). Post hoc analysis showed that there was a significant difference in NT-proBNP levels between those with vitamin D deficiency and those with normal vitamin D levels (P = 0.012). Conclusion: There is an association between vitamin D and left ventricular function and NT-proBNP levels in children with thalassemia major and iron overload. Vitamin D can be considered in patients with thalassemia having vitamin D deficiency. PMID:27212846

  17. ["Pro Ana": Psychodynamic References for Anorexia Nervosa].

    PubMed

    Siefert, Linda

    2017-02-01

    "Pro Ana": Psychodynamic References for Anorexia Nervosa The internet-based phenomenon "Pro Ana" refers to the eating disorder anorexia nervosa in a positive way. To understand what the phenomenon "Pro Ana" represents, the websites are used as a starting point of the current analysis. Based on these results, similarities and differences between "Pro Ana" and the eating disorder anorexia nervosa are discussed. Furthermore psychodynamic references for anorexia nervosa are derived and finally their importance for treatment motivation will be considered.

  18. Corner Office: ProQuest's Marty Kahn

    ERIC Educational Resources Information Center

    Fialkoff, Francine; Oder, Norman

    2009-01-01

    In a scant three years at ProQuest, Marty Kahn, CEO, has moved a company coming out of a financial morass back onto solid ground. He came on board after the purchase of ProQuest Information and Learning by the (mostly) privately owned Cambridge Information Group in late 2006 and the merger of ProQuest and CSA to form ProQuest CSA. (It's now just…

  19. Rat pro-opiomelanocortin contains sulfate

    SciTech Connect

    Hoshina, H.; Hortin, G.; Boime, I.

    1982-07-02

    Intermediate lobes isolated from rat pituitary glands incorporated (/sup 35/S)sulfate into pro-opiomelanocortin and other adrenocorticotropic hormone-containing peptides. Incubation of intermediate lobes in medium containing the arginine analog canavanine inhibited the cleavage of pro-opiomelanocortin into smaller products. Pro-opiomelanocortin that accumulated in the presence of canavanine was also sulfated.

  20. Evaluation by N-terminal prohormone of brain natriuretic peptide concentrations and ross scoring of the efficacy of digoxin in the treatment of heart failure secondary to congenital heart disease with left-to-right shunts.

    PubMed

    Elkiran, Ozlem; Sandikkaya, Ayse; Kocak, Gulendam; Karakurt, Cemsit; Taskapan, Cagatay; Yologlu, Saim

    2013-10-01

    This study aimed to evaluate the effectiveness of digoxin in children with heart failure secondary to left-to-right shunt lesions and normal left ventricular systolic function. The study registered 37 such patients (ages 10 days to 24 months, groups 1 and 2) and used 20 healthy children as a control group (group 3). Left ventricular systolic function, as assessed by conventional echocardiography, was normal in all the subjects. Congestive heart failure was diagnosed by clinical evaluation and modified Ross scoring. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations and complete blood counts were assessed in all the children. Group 1 was treated with digoxin, enalapril, and furosemide and group 2 with enalapril and furosemide. Approximately 1 month after starting treatment, the patients were reevaluated by physical and echocardiographic examinations, modified Ross scoring, plasma NT-proBNP concentrations, and complete blood counts. The pre- and posttreatment Ross scores of group 1 (p = 0.377) and group 2 (p = 0.616) did not differ significantly. The NT-proBNP values in both groups decreased after treatment (p = 0.0001). The pre- and posttreatment NT-proBNP values did not differ significantly in group 1 (p = 0.094)) and group 2 (p = 0.372). The pretreatment NT-proBNP values in groups 1 and 2 (p = 0.0001) were significantly higher than in the control group (p = 0.003). A smaller difference was observed between posttreatment NT-proBNP values in group 1 and the control group (p = 0.045). We found no significant difference between the posttreatment NT-proBNP values of group 2 and those of the control group (p = 0.271). The study showed that both treatments currently used to treat heart failure secondary to congenital heart disease with left-to-right shunts and preserved left ventricular systolic function are effective and do not differ significantly. Thus, digoxin does not provide any extra benefit in the treatment of such patients.

  1. Relationship between expression levels and atherogenesis in scavenger receptor Class B, Type I Transgenics

    SciTech Connect

    Ueda, Yukihiko; Gong, Elaine; Royer, Lori; Cooper, Philip N.; Francone, Omar L; Rubin, Edward M.

    2000-03-15

    Both in vitro and in vivo studies of SR-BI have implicated it as a likely participant in the metabolism of HDL cholesterol. To investigate SR-BI's effect on atherogenesis we examined two lines of SR-BI transgenic mice with high (10-fold increases) and low (2-fold increases) in SR-BI expression in an inbred mouse background hemizygous for a human apo B transgene. Unlike non-HDL cholesterol levels which minimally differed in the various groups of animals, HDL cholesterol levels were inversely related to SR-BI expression. Mice with the low expression SR-BI transgene had a 50% reduction in HDL cholesterol while the high expression SR-BI transgene was associated with two-fold decreases in HDL as well as dramatic alterations in HDL composition and size including the near absence of a-migrating particles as determined by 2-dimensional electrophoresis. The low expression SR-BI/apo B transgenics had more than a two-fold decrease in the development of diet induced fatty streak lesions compared t o the apo B transgenics (4448{+-}1908 {mu}m2/aorta to 10133 {+-} 4035 {mu}m2/aorta; p<0.001), while the high expression SR-BI/apo B transgenics had an atherogenic response similar to that of the apo B transgenics (14692{+-}7238 {mu}m2/aorta) but three-fold greater than the low SR-BI/apo B mice (p<0.001). The prominent anti-atherogenic effect of moderate SR-BI expression provides in vivo support for the hypothesis that HDL functions to inhibit atherogenesis through its interactions with SR-BI in facilitating reverse cholesterol transport. The failure of the high SR-BI/apo B transgenics to have similar or even greater reductions in atherogenesis suggests that the changes resulting from extremely high SR-BI expression including dramatic changes in lipoproteins may have both pro- and anti-atherogenic consequences illustrating the complexity of the relationship between SR-BI and atherogenesis.

  2. Preparation of recombinant thioredoxin fused N-terminal proCNP: Analysis of enterokinase cleavage products reveals new enterokinase cleavage sites.

    PubMed

    Liew, Oi Wah; Ching Chong, Jenny Pek; Yandle, Tim G; Brennan, Stephen O

    2005-06-01

    C-type natriuretic peptide (CNP) acts as a paracrine hormone to dilate blood vessels and is also required for the growth of long bones. In vivo, CNP is produced by cleavage from the C-terminal end of a larger proCNP peptide. The remaining N-terminal proCNP fragment (NT-proCNP) escapes into the circulation where its concentration is much higher than that of CNP due presumably to a lower clearance rate. Our strategy to obtain large quantities of pure NT-proCNP for further physiological investigations was to express it as a fusion protein with His(6)-tagged thioredoxin followed by cleavage using enterokinase to yield NT-proCNP alone. We have successfully designed and artificially synthesized the coding sequence specifying both mouse and human NT-proCNP with built-in codon bias towards Escherichia coli codon preference. An enterokinase recognition sequence was incorporated immediately upstream of the NT-proCNP coding sequence to allow the fusion protein to be cleaved without leaving any extra residues on the NT-proCNP peptide. High levels of fusion proteins were obtained, constituting 50-58% of total bacterial proteins. Greater than 90% of recombinant thioredoxin/NT-proCNP was expressed in the soluble form and purified to near homogeneity in a single chromatographic step using nickel as the metal ion in IMAC. A time course analysis of the products released from enterokinase cleavage of the recombinant proteins by ESI-MS revealed three sensitive secondary cleavage sites: two were located on vector-associated sequences linking the thioredoxin moiety and NT-proCNP, and one at the C-terminal end of NT-proCNP. Clearly, substrate specificity of both the native and recombinant forms of enterokinase for the recognition sequence DDDDK was by no means exclusive. Hydrolysis at the unexpected LKGDR site located towards the carboxyl end on NT-proCNP was significantly more efficient than at the internally sited DDDDK target sequence. However, when this same sequence was sited

  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. A Novel Role for Brain Natriuretic Peptide: Inhibition of IL-1β Secretion via Downregulation of NF-kB/Erk 1/2 and NALP3/ASC/Caspase-1 Activation in Human THP-1 Monocyte

    PubMed Central

    Antognelli, Cinzia; Talesa, Vincenzo Nicola

    2017-01-01

    Interleukin-1β (IL-1β) is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1β processing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1β and its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents. IL-1β is a strong regulator of Brain Natriuretic Peptide (BNP), a hormone involved in cardiovascular homeostasis by guanylyl cyclase Natriuretic Peptide Receptor (NPR-1). An emerging role of BNP in inflammation and immunity, although proposed, remains largely unexplored. Here, we newly demonstrated that, in human THP-1 monocytes, LPS/ATP-induced IL-1β secretion is strongly inhibited by BNP/NPR-1/cGMP axis at all the molecular mechanisms that tightly control its production and release, NF-kB, ERK 1/2, and all the elements of NALP3/ASC/Caspase-1 inflammasome cascade, and that NALP3 inflammasome inhibition is directly related to BNP deregulatory effect on NF-kB/ERK 1/2 activation. Our findings reveal a novel potent anti-inflammatory and immunomodulatory role for BNP and open new alleys of investigation for a possible employment of this endogenous agent in the treatment of inflammatory/immune-related and IL-1β/NF-kB/ERK1/2/NALP3/ASC/Caspase-1-associated diseases. PMID:28331244

  7. 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

  8. 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.

  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. ProMAT: protein microarray analysis tool

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Varnum, Susan M.; Anderson, Kevin K.; Bollinger, Nikki; Zangar, Richard C.

    2006-04-04

    Summary: ProMAT is a software tool for statistically analyzing data from ELISA microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code. Availability: ProMAT is available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version 1.5.0 and R version 1.9.1 (or more recent versions) which are distributed with the tool.

  11. NT-proBNP <95 ng/l can exclude pulmonary hypertension on echocardiography at diagnostic workup in patients with interstitial lung disease

    PubMed Central

    Andersen, Charlotte; Mellemkjær, Søren; Hilberg, Ole; Bendstrup, Elisabeth

    2016-01-01

    Background Pulmonary hypertension (PH) is a serious complication to interstitial lung disease (ILD) and has a poor prognosis. PH is often diagnosed by screening with echocardiography followed by right heart catheterisation. A previous study has shown that a value of NT-pro-brain natriuretic peptide (NT-proBNP) <95 ng/l could be used to rule out PH in patients with ILD. Aim To evaluate this rule-out test for PH in a new cohort of incident patients with ILD. Methods An established database with data from 148 consecutive patients referred from January 2012 to October 2014 was used to identify patients and obtain data from echocardiography, NT-proBNP, diagnosis and lung function. Signs of PH on echocardiography were defined as a tricuspid pressure gradient (TR) ≥40 mmHg, decreased right ventricular systolic function or dilatation. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of NT-proBNP >95 ng/l for signs of PH on echocardiography were calculated. The study was approved by the Danish Health Authority. Results In 118 patients, data from both echocardiography and measurements of NT-proBNP were available. Eleven of these were screened positive for PH on echocardiography. Sensitivity, specificity, NPV and PPV of NT-proBNP <95 ng/l for PH were 100, 44, 16 and 100%, respectively. Furthermore, no patients with left heart failure as the cause of dyspnoea were missed using this cut-off value. Conclusion NT-proBNP <95 ng/l precludes a positive echocardiographic screen for PH in ILD patients at referral for diagnostic workup. PMID:27478030

  12. Variability of NT‐proBNP plasma and urine levels in patients with stable heart failure: a 2‐year follow‐up study

    PubMed Central

    Cortés, Raquel; Rivera, Miguel; Salvador, Antonio; Bertomeu, Vicente; de Burgos, Fernando García; Roselló‐Lletí, Esther; Portolés, Manuel; Payá, Rafael; Martínez‐Dolz, Luis; Climent, Vicente

    2007-01-01

    Objectives To examine N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) variability in plasma and urine samples of patients with stable heart failure (HF) during a 24‐month follow‐up. Design Prospective study. Setting Teaching hospital based study. Patients 74 clinically and functionally stable patients (NYHA class 2±0.5) out of 114 patients diagnosed with HF were followed up, and NT‐proBNP plasma and urine levels were measured at baseline, 12 and 24 months. Results Significant differences in mean urinary levels (p<0.01) were found during follow‐up, but no changes were found in plasma. Bland–Altman plots showed few variations in plasma percentages in the three intervals (stage I–basal; stage II–stage I; stage II–basal) with a coefficient of reproducibility (CR) of 22%, 21% and 25%, respectively. Changes in NT‐proBNP urinary levels had a CR of 7.1%, 6.8% and 9.4% at the three intervals, respectively. A good correlation was found between plasma and urinary levels of NT‐proBNP (p<0.001) and between the different NT‐proBNP plasma (p<0.001) and urine measurements (p<0.001). Conclusions NT‐proBNP plasma and urine levels show good stability in a 24‐month follow‐up of patients with stable heart failure. Thus, assessment of urinary and plasma NT‐proBNP concentrations may be a useful tool for monitoring patients with HF during follow‐up. The results suggest that variations in peptide concentrations exceeding 22% in plasma and 7% in urine in a 12‐month follow‐up and 25% and 9% in a 24‐month follow‐up may indicate pathophysiological changes. PMID:17488774

  13. 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

  14. 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

  15. 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

  16. 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.

  17. proPSA — EDRN Public Portal

    Cancer.gov

    ProPSA (-2), or [-2]proPSA, is a PSA isoform which has a leader peptide (-2) amino acids at its N terminal region and does not interact with ACT or alpha-2-macroglobulin or spermidine and therefore is detected as a separate isoform. ProPSA is produced primarily in the peripheral zone of the prostate gland and therefore is very useful in distinguishing between prostate cancer patients with PSA range of 2-10, from those who have BPH. Percent proPSA is the ratio of proPSA to free PSA. In July 2012 the FDA approved an assay measuring levels of [-2]proPSA for monitoring and diagnostic purposes.

  18. Clinton administration shows pro-gas bias

    SciTech Connect

    Patrick, L.

    1993-02-01

    President Bill Clinton's cabinet appointments signify a strong shift to more pro-environmental, proconservation energy policies. Clinton signaled a pro-consumer, pro-conservation tilt for the Energy Department with the nomination of Hazel O'Leary, an executive vice president of Northern States Power Co., Minneapolis, to be Secretary of Energy. O'Leary will be responsible for implementing the new National Energy Policy Act, which must resolve a number of energy efficiency and conservation issues.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Acute changes in endocrine and fluid balance markers during high-intensity, steady-state, and prolonged endurance running: unexpected increases in oxytocin and brain natriuretic peptide during exercise.

    PubMed

    Hew-Butler, Tamara; Noakes, Timothy D; Soldin, Steven J; Verbalis, Joseph G

    2008-12-01

    Maintenance of fluid homeostasis during periods of heightened physical stress can be best evaluated in humans using exercise as a model. Although it is well established that arginine vasopressin (AVP), aldosterone and atrial natriuretic peptide (ANP) are the principle hormones regulating fluid balance at rest, the potential contributions of other related endocrine factors, such as oxytocin (OT) and brain natriuretic peptide (BNP), have not been well described during exercise. Seven endurance-trained runners completed three separate running trials: a maximal test to exhaustion (high intensity), a 60-min treadmill run (steady state), and a 56 km ultramarathon (prolonged endurance exercise). Statistically significant pre- to post-run increases were found only following the ultramarathon in [AVP](p) (1.9 vs 6.7 pg/ml; P<0.05), [OT](p) (1.5 vs 3.5 pg/ml; P<0.05), [NT-proBNP](p) (23.6 vs 117.9 pg/ml; P<0.01), [interleukin 6](p) (4.0 vs 59.6 pg/ml; P<0.05), [cortisol](p) (14.6 vs 32.6 microg/ml; P<0.01), [corticosterone](p) (652.8 vs 3491.4 ng/ml; P<0.05) and [11-deoxycortisol](p) (0.1 vs 0.5 microg/ml; P<0.05) while a significant post-run increase in [aldosterone](p) was documented after high-intensity (4.9 vs 12.5 ng/ml; P<0.05), steady-state (6.1 vs 16.9 ng/ml; P<0.05) and prolonged endurance running (2.6 vs 19.7 ng/ml; P<0.05). Similarly, changes in fluid balance parameters were significantly different between the ultramarathon versus high-intensity and steady-state running with regard to plasma volume contraction (less % contraction), body weight loss (increased % weight loss), plasma [Na(+)] Delta (decreased from baseline), and urine osmolality Delta (increase from baseline). Hypothetically driven relationships between [OT](p) and [AVP](p) (r=0.69; P<0.01) and between [NT-proBNP](p) Delta and plasma [Na(+)] Delta (r=-0.79; P<0.001)--combined with the significant and unexpected pre- to post-race increases after prolonged endurance exercise--allows for possible

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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).

  9. 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.

  10. Serial measurement of NT-proBNP predicts adverse cardiovascular outcome in children with primary myocardial dysfunction and acute decompensated heart failure (ADHF)

    PubMed Central

    Medar, Shivanand; Hsu, Daphne T.; Ushay, H. Michael; Lamour, Jacqueline M.; Cohen, Hillel W; Killinger, James S.

    2015-01-01

    Introduction In children, elevated amino terminal pro B-type naturetic peptide (NT-proBNP) levels are associated with impaired heart function. The predictive value of serial monitoring of NT-proBNP levels in acute decompensated heart failure (ADHF) is unclear. Methods This prospective observational study enrolled patients ≤ 21 years with primary myocardial dysfunction and ADHF. NT-proBNP levels were obtained on enrollment (D0), day 2 (D2) and day 7 (D7). Clinical, laboratory and imaging data were collected on enrollment. CV outcome was defined as Heart Transplant (HTx), Ventricular Assist Device (VAD) placement, Extracorporeal Membrane Oxygenation or death at 1 year after admission. NT-proBNP levels and the percent change from D0 to D2 and D0 to D7 were calculated and compared between those with and without adverse cardiovascular (ACV) outcome. Results Sixteen consecutive patients were enrolled. ACV outcome occurred in 6 (37.5%, 4 HTx and 2 VAD). In patients with an ACV outcome, median NT-ProBNP levels at D7 were significantly higher (7,365 Vs. 1,196 pg/ml; p= 0.02) and the percent decline in NT-proBNP was significantly smaller (28% vs. 73%, p=0.02) compared to those without an ACV outcome. ROC curve analysis revealed that a less than 55% decline in NT-proBNP levels at D7 had a sensitivity and specificity of 83% and 90% respectively in predicting an ACV [AUC 0.86, CI (0.68,1.0), p=0.02]. Conclusions In conclusion, children with primary myocardial dysfunction and ADHF, a persistently elevated NT-proBNP and/or a lesser degree of decline in NT-proBNP during the first week of presentation were strongly associated with ACV outcome. Serial NT-proBNP monitoring may allow the early identification of children at risk for worse outcome. PMID:25856472

  11. Elevated NT-proBNP Levels are Associated with Poor Cognitive Function in Community-Dwelling Older Adults: Results from the Rancho Bernardo Study

    PubMed Central

    Daniels, Lori B.; Laughlin, Gail A.; Kritz-Silverstein, Donna; Clopton, Paul; Chen, Wei-Chung; Maisel, Alan S.; Barrett-Connor, Elizabeth

    2011-01-01

    Background Natriuretic peptides (NP’s) have prognostic value across a wide spectrum of cardiovascular diseases and may predict cognitive dysfunction in patients with cardiovascular disease even in the absence of prior stroke. Little is known about the association of NP’s with cognitive function in community-dwelling adults. We assessed the association between NT-proBNP levels and cognitive function in community-dwelling ambulatory older adults in the Rancho Bernardo Study. Methods We studied 950 men and women, aged 60 years and older, who attended a research clinic visit where a medical history and examination were performed, and blood for cardiovascular disease risk factors and NT-proBNP levels were obtained. Three cognitive function tests were administered: Mini Mental State Exam (MMSE), Trail-Making Test B (Trails B), and Category Fluency. Results Participants with high NT-proBNP levels (≥450 pg/mL, n=198) were older and had a higher prevalence of coronary heart disease (12% vs. 30%), and stroke (5% vs. 11%) (both p’s≤0.001). In unadjusted analyses, all three cognitive function test scores were significantly associated with NT-proBNP levels (p<0.001). After adjusting for age, sex, education, hypertension, body mass index, exercise, alcohol use, smoking, low density lipoprotein cholesterol, creatinine clearance, and prior cardiovascular disease, elevated NT-proBNP levels remained independently associated with poor cognitive performance on MMSE (odds ratio [95% confidence interval] 2.0 [1.1–3.6], p=0.02) and Trails B (1.7 [1.2–2.7], p=0.01), but not Category Fluency (1.4 [0.9–2.2], p=0.19). Results were unchanged after excluding the 6% of participants with a history of stroke. Conclusions NT-proBNP levels were strongly and independently associated with poor cognitive function in community-dwelling older adults. PMID:21683832

  12. 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.

  13. AnswerPro: Designing to Motivate Interaction

    ERIC Educational Resources Information Center

    AlSugair, Balsam; Hopkins, Gail; FitzGerald, Elizabeth; Brailsford, Tim

    2014-01-01

    This paper describes the design and initial testing of AnswerPro, a mobile academic peer support system for school pupils aged 11-16 years. AnswerPro is a mobile optimised web application that enables pupils to seek support with school work from knowledgeable peers on various subjects. This paper presents research findings from the project, and in…

  14. Integrated Programs and Pro-Environmental Behaviour

    ERIC Educational Resources Information Center

    Smith, Tiffany

    2008-01-01

    Research suggested that "nature experience as an education method played a role in developing environmental value and attitudes, and was influential in pro-environmental behaviour." Few of these studies however, assessed the long-term influences of outdoor education experiences on participants' pro-environmental behaviour. The Outward…

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Pro-Anorexia and Pro-Recovery Photo Sharing: A Tale of Two Warring Tribes

    PubMed Central

    Yom-Tov, Elad; Weber, Ingmar; Crain, Steven P

    2012-01-01

    Background There is widespread use of the Internet to promote anorexia as a lifestyle choice. Pro-anorexia content can be harmful for people affected or at risk of having anorexia. That movement is actively engaged in sharing photos on social networks such as Flickr. Objective To study the characteristics of the online communities engaged in disseminating content that encourages eating disorders (known as “pro-anorexia”) and to investigate if the posting of such content is discouraged by the posting of recovery-oriented content. Methods The extraction of pro-anorexia and pro-recovery photographs from the photo sharing site Flickr pertaining to 242,710 photos from 491 users and analyzing four separate social networks therein. Results Pro-anorexia and pro-recovery communities interact to a much higher degree among themselves than what is expected from the distribution of contacts (only 59-72% of contacts but 74-83% of comments are made to members inside the community). Pro-recovery users employ similar words to those used by pro-anorexia users to describe their photographs, possibly in order to ensure that their content appears when pro-anorexia users search for images. Pro-anorexia users who are exposed to comments from the opposite camp are less likely to cease posting pro-anorexia photographs than those who do not receive such comments (46% versus 61%), and if they cease, they do so approximately three months later. Our observations show two highly active communities, where most interaction is within each community. However, the pro-recovery community takes steps to ensure that their content is visible to the pro-anorexia community, both by using textual descriptions of their photographs that are similar to those used by the pro-anorexia group and by commenting to pro-anorexia content. The latter activity is, however, counterproductive, as it entrenches pro-anorexia users in their stance. Conclusions Our results highlight the nature of pro-anorexia and pro

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Manduca sexta proprophenoloxidase activating proteinase-3 (PAP3) stimulates melanization by activating proPAP3, proSPHs, and proPOs

    PubMed Central

    Wang, Yang; Lu, Zhiqiang; Jiang, Haobo

    2014-01-01

    Melanization participates in various insect physiological processes including antimicrobial immune responses. Phenoloxidase (PO), a critical component of the enzyme system catalyzing melanin formation, is produced as an inactive precursor prophenoloxidase (proPO) and becomes active via specific proteolytic cleavage by proPO activating proteinase (PAP). In Manduca sexta, three PAPs can activate proPOs in the presence of two serine proteinase homologs (SPH1 and SPH2). While the hemolymph proteinases (HPs) that generate the active PAPs are known, it is unclear how the proSPHs (especially proSPH1) are activated. In this study, we isolated from plasma of bar-stage M. sexta larvae an Ile-Glu-Ala-Arg-p-nitroanilide hydrolyzing enzyme that cleaved the proSPHs. This proteinase, PAP3, generated active SPH1 and SPH2, which function as cofactors for PAP3 in proPO activation. Cleavage of the purified recombinant proSPHs by PAP3 yielded 38 kDa bands similar in mobility to the SPHs formed in vivo. Surprisingly, PAP3 also can activate proPAP3 to stimulate melanization in a direct positive feedback loop. The enhanced proPO activation concurred with the cleavage activation of proHP6, proHP8, proPAP1, proPAP3, proSPH1, proSPH2, proPOs, but not proHP14 or proHP21. These results indicate that PAP3, like PAP1, is a key factor of the self-reinforcing mechanism in the proPO activation system, which is linked to other immune responses in M. sexta. PMID:24768974

  12. 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

  13. Technology evaluation: PRO-542, Progenics Pharmaceuticals inc.

    PubMed

    Mukhtar, M; Parveen, Z; Pomerantz, R J

    2000-12-01

    Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the Aaron Diamond AIDS Research Center (ADARC) in New York and the Center for Disease Control and Prevention in Atlanta [178410]. In February 2000, Progenics and Genzyme Transgenics Corp signed an agreement to continue the development of a transgenic source of PRO-542. Genzyme will develop transgenic goats that produce PRO-542 in their milk in exchange for undisclosed fees and milestone payments. Genzyme will supply PRO-542 to Progenics for clinical trials with a possibility for eventual commercial supply [357291]. Following on from this, in October 2000, Progenics received an SBIR grant to fund a two-year project with Genzyme Transgenics into the development of cost-effective methods for the manufacture of PRO-542, by optimization of the production of the drug in the milk of transgenic dairy animals [385982]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of PRO-542 and GMK (Progenics Pharmaceuticals) in 2002 [390063].

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

    PubMed Central

    Schellings, Dirk AAM; Adiyaman, Ahmet; Dambrink, Jan-Henk E; Gosselink, AT Marcel; Kedhi, Elvin; Roolvink, Vincent; Ottervanger, Jan Paul; van’t Hof, Arnoud WJ

    2016-01-01

    Background The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts outcome in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS). Whether NT-proBNP has incremental prognostic value beyond established risk strategies is still questionable. Purpose To evaluate the predictive value of NT-proBNP for 30-day mortality over and beyond the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) risk scores in patients with NSTE-ACS. Methods Patients included in our ACS registry were candidates. NT-proBNP levels on admission were measured and the GRACE and TIMI risk scores were assessed. We compared the predictive value of NT-proBNP to both risk scores and evaluated whether NT-proBNP improves prognostication by using receiver operator curves and measures of discrimination improvement. Results A total of 1324 patients were included and 50 patients died during follow-up. On logistic regression analysis NT-proBNP and the GRACE risk score (but not the TIMI risk score) both independently predicted mortality at 30 days. The predictive value of NT-proBNP did not differ significantly compared to the GRACE risk score (area under the curve [AUC]) 0.85 vs 0.87 p=0.67) but was considerably higher in comparison to the TIMI risk score (AUC 0.60 p<0.001). Adjustment of the GRACE risk score by adding NT-proBNP did not improve prognostication: AUC 0.86 (p=0.57), integrated discrimination improvement 0.04 (p=0.003), net reclassification improvement 0.12 (p=0.21). Conclusion In patients with NSTE-ACS, NT-proBNP and the GRACE risk score (but not the TIMI risk score) both have good and comparable predictive value for 30-day mortality. However, incremental prognostic value of NT-proBNP beyond the GRACE risk score could not be demonstrated. PMID:27920547

  3. Helical computerized tomography and NT-proBNP for screening of right ventricular overload on admission and at long term follow-up of acute pulmonary embolism

    PubMed Central

    2012-01-01

    Background Right ventricular dysfunction (RVD) in acute pulmonary embolism (APE) can be assessed with helical computerized tomography (CT) and transthoracic echocardiography (TTE). Signs of RVD and elevated natriuretic peptides like NT-proBNP and cardiac troponin (TnT) are associated with increased risk of mortality. However, the prognostic role of both initial diagnostic strategy and the use of NT-proBNP and TnT for screening for long-term probability of RVD remains unknown. The aim of the study was to determine the role of helical CT and NT-proBNP in detection of RVD in the acute phase. In addition, the value of NT-proBNP for ruling out RVD at long-term follow-up was assessed. Methods Sixty-three non-high risk APE patients were studied. RVD was assessed at admission in the emergency department by CT and TTE, and both NT-proBNP and TnT samples were taken. These, excepting CT, were repeated seven months later. Results At admission RVD was detected by CT in 37 (59 %) patients. RVD in CT correlated strongly with RVD in TTE (p < 0.0001). NT-proBNP was elevated (≥ 350 ng/l) in 32 (86 %) patients with RVD but in only seven (27 %) patients without RVD (p < 0.0001). All the patients survived until the 7-month follow-up. TTE showed persistent RVD in 6 of 63 (10 %) patients who all had RVD in CT at admission. All of them had elevated NT-proBNP levels in the follow-up compared with 5 (9 %) of patients without RVD (p < 0.0001). Conclusions TTE does not confer further benefit when helical CT is used for screening for RVD in non-high risk APE. All the patients who were found to have RVD in TTE at seven months follow-up had had RVD in the acute phase CT as well. Thus, patients without RVD in diagnostic CT do not seem to require further routine follow-up to screen for RVD later. On the other hand, persistent RVD and thus need for TTE control can be ruled out by assessment of NT-proBNP at follow-up. A follow-up protocol based on these findings is suggested. PMID:22559861

  4. Variability of NT-proBNP and Its Relationship with Inflammatory Status in Patients with Stable Essential Hypertension: A 2-Year Follow-Up Study

    PubMed Central

    Roselló-Lletí, Esther; Calabuig, Jose R.; Morillas, Pedro; Cortés, Raquel; Martínez-Dolz, Luis; Almenar, Luis; González-Juanatey, Jose R.; Lauwers, Catheline; Salvador, Antonio; Portolés, Manuel; Bertomeu, Vicente; Rivera, Miguel

    2012-01-01

    Background The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited. Methodology/Principal Findings 220 clinically and functionally asymptomatic stable patients (age 59±13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p<0.0001 and r = 0.59, p<0.0001) and stage I versus stage II (r = 0.86, p<0.0001 and r = 0.56, p<0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p<0.0001) and IL-6 (p<0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP. Conclusions/Significance This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment

  5. 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

  6. Induction of systemic disease resistance in Nicotiana benthamiana by the cyclodipeptides cyclo (l-Pro-l-Pro) and cyclo (d-Pro-d-Pro).

    PubMed

    Wu, Liming; Wu, Huijun; Chen, Lina; Zhang, Hongyue; Gao, Xuewen

    2017-01-01

    Cyclodipeptides, formed from two amino acids by cyclodehydration, are produced naturally by many organisms, and are known to possess a large number of biological activities. In this study, we found that cyclo (l-Pro-l-Pro) and cyclo (d-Pro-d-Pro) (where Pro is proline) could induce defence responses and systemic resistance in Nicotiana benthamiana. Treatment with the two cyclodipeptides led to a reduction in disease severity by Phytophthora nicotianae and Tobacco mosaic virus (TMV) infections compared with controls. Both cyclopeptides triggered stomatal closure, induced reactive oxygen species production and stimulated cytosolic calcium ion and nitric oxide production in guard cells. In addition, the application of cyclodipeptides significantly up-regulated the expression of the plant defence gene PR-1a and the PR-1a protein, and increased cellular salicylic acid (SA) levels. These results suggest that the SA-dependent defence pathway is involved in cyclodipeptide-mediated pathogen resistance in N. benthamiana. We report the systemic resistance induced by cyclodipeptides, which sheds light on the potential of cyclodipeptides for the control of plant diseases.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. [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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. C-type natriuretic peptide is closely associated to obesity in Caucasian adolescents.

    PubMed

    Del Ry, Silvia; Cabiati, Manuela; Bianchi, Vanessa; Caponi, Laura; Maltinti, Maristella; Caselli, Chiara; Kozakova, Michaela; Palombo, Carlo; Morizzo, Carmela; Marchetti, Sara; Randazzo, Emioli; Clerico, Aldo; Federico, Giovanni

    2016-09-01

    CNP is a natural regulator of adipogenesis playing a role in the development of obesity in childhood. Aim of the study was to evaluate CNP plasma levels in normal-weight (N), overweight (OW) and obese adolescents (O). Eighty two subjects (age:12.8±2.4, years) without cardiac dysfunction were enrolled and CNP plasma levels were measured by RIA. NT-proBNP, MR-proANP, AGEs, reactive hyperemia index (RHI) and standard clinical chemistry parameters were also measured. O and OW adolescents had higher values of BMI and fat mass than N. CNP levels were significantly lower in OW:4.79[3.29-21.15] and O:3.81[1.55-13.4] than in N:13.21[7.6-37.8]; p<0.0001N vs O, p=0.0003N vs OW). LogCNP values correlated significantly and inversely with BMI z-score, FM%, TF% and circulating levels of CRP, insulin, total cholesterol, LDL, and triglycerides, in addition to an inverse relationship with skin AGEs and a direct correlation with RHI. LogCNP was also inversely associated with LogNT-proBNP and LogMR-proANP values. Using ROC analysis the risk of obesity resulted significantly (p≪0.0001) associated with CNP values (AUC=0.9724). These results suggest that CNP may play a more important role than BNP and ANP related peptides, as risk marker of obesity, in addition to its involvement in adipogenesis and endothelial dysfunction.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Pro-Am Collaboration and the AAVSO

    NASA Astrophysics Data System (ADS)

    Henden, A.

    2006-04-01

    Professionals need to be aware that there is a valuable resource available and waiting to be used -- the amateur astronomy community. We give some examples of how pro-am collaborations have worked in the past, indicate the advantages and disadvantages of such collaborations, and suggest methods by which a professional can find and work effectively with amateur astronomers.

  9. Pocahontas: Problematizing the Pro-Social.

    ERIC Educational Resources Information Center

    Aidman, Amy; Reese, Debbie

    The Disney film "Pocahontas" appears to be an attempt to respond to growing cultural diversity, calls for multiculturalism, and strong female role models in the United States. This paper provides an analysis of the film, examining how Disney's claims to the creation of positive, pro-social representations of women and Native Americans in…

  10. A Pro-Family Income Tax.

    ERIC Educational Resources Information Center

    Carlson, Allan

    1989-01-01

    Discusses the Tax Reform Act of 1986, which doubled the personal exemption, increased the eligibility ceiling for the Earned Income Tax Credit, and reduced marginal income-tax rates. Compares the Act with the Acts of 1948 and 1969. Outlines criteria for a pro-family income tax policy. (BJV)

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Crystal structure of the collagen triple helix model [(Pro-Pro-Gly)(10)](3).

    PubMed

    Berisio, Rita; Vitagliano, Luigi; Mazzarella, Lelio; Zagari, Adriana

    2002-02-01

    The first report of the full-length structure of the collagen-like polypeptide [(Pro-Pro-Gly)(10)](3) is given. This structure was obtained from crystals grown in a microgravity environment, which diffracted up to 1.3 A, using synchrotron radiation. The final model, which was refined to an R(factor) of 0.18, is the highest-resolution description of a collagen triple helix reported to date. This structure provides clues regarding a series of aspects related to collagen triple helix structure and assembly. The strict dependence of proline puckering on the position inside the Pro-Pro-Gly triplets and the correlation between backbone and side chain dihedral angles support the propensity-based mechanism of triple helix stabilization/destabilization induced by hydroxyproline. Furthermore, the analysis of [(Pro-Pro-Gly)(10)](3) packing, which is governed by electrostatic interactions, suggests that charges may act as locking features in the axial organization of triple helices in the collagen fibrils.

  18. 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.

  19. 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.

  20. The pro-oxidant activity of aluminum.

    PubMed

    Exley, Christopher

    2004-02-01

    Aluminum, a non-redox-active metal is, nevertheless, a pro-oxidant both in in vitro preparations and in vivo. It facilitates both superoxide- and iron-driven biological oxidation by mechanisms that remain to be resolved. More than 10 years ago Fridovich and colleagues suggested that the facilitation of superoxide-driven biological oxidation by aluminum was due to an interaction between the metal and the superoxide radical anion (Free Radic. Biol. Med. 13: 79-81; 1992). This thesis has been examined herein and it is concluded that much, if not all, of the pro-oxidant activity of aluminum might be explained by the formation of an aluminum superoxide semireduced radical ion.

  1. [Radiation Anticarcinogenesis by Thiazolidine Pro-drug

    NASA Technical Reports Server (NTRS)

    Warters, Raymond L.; Roberts, Jeanette C.; Fain, Heidi

    1999-01-01

    The original goal of this work was to determine the capacity of selected aminothiols to modulate radiation induced cytotoxicity, mutagenesis and carcinogenesis in a human mammary epithelial cell line. The conclusions from this work are that WR-1065 is the "gold standard" for protection against radiation induced cytotoxicity, mutagenesis and carcinogenesis. While a potent radiation protector, WR-1065 is cytotoxic in vitro and in vivo. Our rationale for a study of the thiazolidine pro-drugs was that these compounds are neither toxic in vitro or in vivo. The results obtained during this funding period indicate that the thiazolidine pro-drugs are as potent as WR-1065 as protectors against radiation induced mutation induction, and thus presumably against radiation induced carcinogenesis. Our results indicate that the thiazolidine prodrugs are excellent candidates to test as non-toxic anticarcinogens for protecting astronauts from cancer induction during space travel.

  2. Cryogenic system for BERLinPro

    SciTech Connect

    Anders, W.; Hellwig, A.; Knobloch, J.; Pflückhahn, D.; Rotterdam, S.

    2014-01-29

    In 2010 Helmholtz-Zentrum Berlin (HZB) received funding to design and build the Berlin Energy Recovery Linac Project BERLinPro. The goal of this compact Energy recovery linac (ERL) is to develop the accelerator physics and technology required to generate and accelerate a 100-mA, 1-mm mrad emittance electron beam. The BERLinPro know-how can then be transferred to various ERL-based applications. All accelerating RF cavities including the electron source are based on superconducting technology operated at 1.8 K. A Linde L700 helium liquefier is supplying 4.5 K helium. The subatmospheric pressure of 16 mbar of the helium bath of the cavities will be achieved by pumping with a set of cold compressors and warm vacuum pumps. While the L700 is already in operating, the 1.8 K system and the helium transfer system are in design phase.

  3. 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.

  4. The PRO nurse: advocate for quality care.

    PubMed

    Carroll, M; Maichele, J

    1993-01-01

    Since the inception of the Social Security Amendments of 1983, nurses have assumed expanded roles in ensuring the monitoring of the quality of care received by Medicare beneficiaries. This unique area of nursing practice offers new challenges and employment opportunities for the nurse as a patient advocate. Nurses who are interested in this role may contact state PRO directors or watch for specific recruitment advertisements in nursing magazines.

  5. ProFit: Bayesian galaxy fitting tool

    NASA Astrophysics Data System (ADS)

    Robotham, A. S. G.; Taranu, D.; Tobar, R.

    2016-12-01

    ProFit is a Bayesian galaxy fitting tool that uses the fast C++ image generation library libprofit (ascl:1612.003) and a flexible R interface to a large number of likelihood samplers. It offers a fully featured Bayesian interface to galaxy model fitting (also called profiling), using mostly the same standard inputs as other popular codes (e.g. GALFIT ascl:1104.010), but it is also able to use complex priors and a number of likelihoods.

  6. 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.

  7. 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.

  8. 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

  9. Some problems with pro-competition reforms.

    PubMed

    Agich, G J; Begley, C E

    1985-01-01

    As the search for effective cost-containment policies continues, health care reform along pro-competition lines has gained considerable backing in the United States. By offering market competition to achieve allocational efficiency and vouchers and tax credits to achieve distributional equity, pro-competition reforms appear to satisfy what many believed were incommensurable goals. A critical review of this strategy reveals two practical difficulties, however. The first concerns the ambiguity arising from the proposals' reliance on the concept of equal access to some basic level of health care as its distributional objective and the second concerns the ethical dilemma arising from the proposals' reliance on physicians as rationers of health care. In considering the distributional goal of guaranteeing access to a basic minimum of health care, we argue that, despite its theoretical attractiveness, there exists no acceptable way of determining or justifying its content, and without a clear definition of the basic minimum there is no guarantee that any equity objective will be achieved under the pro-competition strategy. With regard to the use of physicians and other providers as society's gatekeepers, we point out that this role is in direct conflict with traditional responsibilities that patients expect providers to assume. Requiring doctors to ration services in response to market incentives may further erode the trust relationship between physicians and patients, and clearly puts the more seriously ill at a disadvantage.

  10. Calibrating the Prominence Magnetometer (ProMag)

    NASA Astrophysics Data System (ADS)

    Fox, Lewis; Casini, R.

    2013-07-01

    The Prominence Magnetometer (ProMag) is a dual-channel, dual-beam, slit-scanning, full Stokes spectro-polarimeter designed by the High Altitude Observatory at the National Center for Atmospheric Research (HAO/NCAR) for the study of the magnetism of solar prominences and filaments. It was deployed in August 2009 at the 40 cm coronagraph of the Evans Solar Facility (ESF) of the National Solar Observatory on Sacramento Peak (NSO/SP). In its standard mode of operation it acquires spectro-polarimetric maps of solar targets simultaneously in the two chromospheric lines of He I at 587.6 nm and 1083.0 nm. Since August 2011 ProMag has operated in “patrol mode” with a dedicated observer. We aim to routinely measure the vector magnetic field in prominences. The electro-optic modulator and polarization analyzer are integrated into a single mechanical unit located at the coude feed of the telescope. This location was necessary for proper co-alignment of the dual beams, but complicates the precise polarimeter calibration necessary to achieve the sensitivity required for prominence measurements (< 10^-3). At this sensitivity, small variations in optical alignment can become significant. We present a calibration method for ProMag, using a polarizer and retarder at coronagraph prime focus. Calibrations are recorded before and after observations. We discuss the success of this method and its limitations.

  11. 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.

  12. ProUCL version 4.00.04 Documentation Downloads

    EPA Pesticide Factsheets

    ProUCL Version 4.00.04 is an upgrade of ProUCL Version 4.0 (EPA, 2007). ProUCL 4.00.02 contains statistical methods to address various environmental issues for both full data sets without nondetects and for data sets with NDs (also known as left-censored d

  13. c[D-pro-Pro-D-pro-N-methyl-Ala] adopts a rigid conformation that serves as a scaffold to mimic reverse-turns.

    PubMed

    Arbor, Sage; Kao, Jeff; Wu, Yun; Marshall, Garland R

    2008-01-01

    Naturally occurring cyclic tetrapeptides (CTPs) such as tentoxin (Halloin et al., Plant Physiol 1970, 45, 310-314; Saad, Phytopathology 1970, 60, 415-418), ampicidin (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147), HC-toxin (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447), and trapoxin (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328; Itazaki et al., J Antibiot (Tokyo) 1990, 43, 1524-1532) have a wide range of biological activity and potential use ranging from herbicides (Walton, Proc Natl Acad Sci USA 1987, 84, 8444-8447; Judson, J Agric Food Chem 1987, 35, 451-456) to therapeutics (Loiseau, Biopolymers 2003, 69, 363-385) for malaria (Darkin-Rattray, Proc Natl Acad Sci USA 1996, 93, 13143-13147) and cancer (Yoshida and Sugita, Jpn J Cancer Res 1992, 83, 324-328). To elucidate scaffolds that have few low-energy conformations and could serve as semirigid reverse-turn mimetics, the flexibility of CTPs was determined computationally. Four analogs of cyclic tetraproline c[Pro-pro-Pro-pro] with alternating L- and D-prolines, namely c[pro-Pro-pro-NMe-Ala], c[pip-Pro-pip-Pro], c[pro-Pip-pro-Pro], and c[Ala-Pro-pip-Pro] were synthesized and characterized by NOESY NMR. Both molecular mechanics and Density Functional Theory quantum calculations found these head-to-tail CTPs to be constrained to one or two relatively stable conformations. NMR structures, while not always yielding the same lowest energy conformation as expected by in silico predictions, confirmed only one or two highly populated solution conformations for all four peptides examined. c[pro-Pro-pro-NMe-Ala] was shown to have a single all trans-amide bond conformation from both in silico predictions and NMR characterization, and to be a reverse-turn mimetic by overlapping four Calpha-Cbeta bonds with those for approximately 6.5% (Tran, J Comput Aided Mol Des 2005, 19, 551-566) of reverse-turns in the Protein Data Bank PDB with a RMSD of 0.57 A.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Perl Embedded in PTC's Pro/ENGINEER, Version 1

    SciTech Connect

    2003-12-22

    Pro-PERL (AKA Pro/PERL) is a Perl extension to the PTC Pro/TOOLKIT API to the PTC Pro/ENGINEER CAD application including an embedded interpreter. It can be used to automate and customize Pro/ENGINEER, create Vendor Neutral Archive (VNA) format files and re-create CAD models from the VNA files. This has applications in sanitizing classified CAD models created in a classified environment for transfer to an open environment, creating template models for modification to finished models by non-expert users, and transfer of design intent data to other modeling technologies.

  5. 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

  6. BDNF pro-peptide regulates dendritic spines via caspase-3

    PubMed Central

    Guo, J; Ji, Y; Ding, Y; Jiang, W; Sun, Y; Lu, B; Nagappan, G

    2016-01-01

    The precursor of brain-derived neurotrophic factor (BDNF) (proBDNF) is enzymatically cleaved, by either intracellular (furin/PC1) or extracellular proteases (tPA/plasmin/MMP), to generate mature BDNF (mBDNF) and its pro-peptide (BDNF pro-peptide). Little is known about the function of BDNF pro-peptide. We have developed an antibody that specifically detects cleaved BDNF pro-peptide, but not proBDNF or mBDNF. Neuronal depolarization elicited a marked increase in extracellular BDNF pro-peptide, suggesting activity-dependent regulation of its extracellular levels. Exposure of BDNF pro-peptide to mature hippocampal neurons in culture dramatically reduced dendritic spine density. This effect was mediated by caspase-3, as revealed by studies with pharmacological inhibitors and genetic knockdown. BDNF pro-peptide also increased the number of ‘elongated' mitochondria and cytosolic cytochrome c, suggesting the involvement of mitochondrial-caspase-3 pathway. These results, along with BDNF pro-peptide effects recently reported on growth cones and long-term depression (LTD), suggest that BDNF pro-peptide is a negative regulator of neuronal structure and function. PMID:27310873

  7. Photoelectron spectrum of PrO-

    NASA Astrophysics Data System (ADS)

    Kafader, Jared O.; Ray, Manisha; Jarrold, Caroline Chick

    2015-08-01

    The photoelectron (PE) spectrum of PrO- exhibits a short 835 ± 20 cm-1 vibrational progression of doublets (210 ± 30 cm-1 splitting) assigned to transitions from the 4f2 [3H4] σ6s2 Ω = 4 anion ground state to the 4f2 [3H4] σ6s Ω = 3.5 and 4.5 neutral states. This assignment is analogous to that of the recently reported PE spectrum of CeO-, though the 82 cm-1 splitting between the 4f [2F2.5] σ6s Ω = 2 and Ω = 3 CeO neutral states could not be resolved [Ray et al., J. Chem. Phys. 142, 064305 (2015)]. The origin of the transition to the Ω = 3.5 neutral ground state is 0.96 ± 0.01 eV, which is the adiabatic electron affinity of PrO. Density functional theory calculations on the anion and neutral molecules support the assignment. The appearance of multiple, irregularly spaced and low-intensity features observed ca. 1 eV above the ground state cannot be reconciled with low-lying electronic states of PrO that are accessible via one-electron detachment. However, neutral states correlated with the 4f2 [3H4] 5d superconfiguration are predicted to be approximately 1 eV above the 4f2 [3H4] σ6s Ω = 3.5 neutral ground state, leading to the assignment of these features to shake-up transitions to the excited neutral states. Based on tentative hot band transition assignments, the term energy of the previously unobserved 4f2 [3H4] σ6s Ω = 2.5 neutral state is determined to be 1840 ± 110 cm-1.

  8. Adiponectinemia controls pro-angiogenic cell therapy.

    PubMed

    Eren, Philippe; Camus, Stéphane; Matrone, Gianfranco; Ebrahimian, Téni G; François, Delphine; Tedgui, Alain; Sébastien Silvestre, Jean; Blanc-Brude, Olivier P

    2009-11-01

    Angiogenic cell therapy with the transplantation of endothelial progenitor cells (EPC) or bone marrow mononuclear cells (BM-MNC) receives considerable attention as an approach to revascularize ischemic tissues. Adiponectin is a circulating hormone produced by the apM1 gene in adipocytes. Adiponectin modulates lipid metabolism and obesity, and it was recently found to promote physiological angiogenesis in response to ischemia. Patients with multiple cardiovascular disease risk factors or myocardial infarction may benefit from progenitor cell therapy, but they display depressed adiponectinemia. We hypothesized that adiponectin stimulation of transplanted cells is critical for their pro-angiogenic function. We aimed to establish whether adiponectinemia in the cell donor or in the cell recipient determines the success of pro-angiogenic cell therapy. In vitro, we found that conditioned media derived from wild-type adipocytes (adipo-CM) or purified adiponectin strongly enhanced BM-MNC survival and proliferation and stimulated EPC differentiation, whereas adipo-CM from apM1-/- adipocytes was one-half less effective. On the other hand, wild-type and apM1-/- BM-MNC displayed similar resistance to apoptosis and proliferation rates. In vivo, wild-type, and apM1-/- BM-MNC induced similar angiogenic reactions in wild-type ischemic hindlimbs. In contrast, wild-type BM-MNC had much diminished effects in apM1-/- ischemic hindlimbs. We concluded that adiponectin enhances BM-MNC survival and proliferation, and adiponectinemia in the cell therapy recipient is essential for the pro-angiogenic benefits of cell therapy. These observations imply that progenitor cell transplantation might only induce angiogenesis in patients with high adiponectinemia.

  9. Educational Opportunities in Pro-Am Collaboration

    NASA Astrophysics Data System (ADS)

    Fienberg, R. T.; Stencel, R. E.

    2006-08-01

    While many backyard stargazers take up the hobby just for fun, many others are attracted to it because of their keen interest in learning more about the universe. The best way to learn science is to do science. Happily, the technology available to today's amateur astronomers — including computer-controlled telescopes, CCD cameras, powerful astronomical software, and the Internet — gives them the potential to make real contributions to scientific research and to help support local educational objectives. Meanwhile, professional astronomers are losing access to small telescopes as funding is shifted to larger projects, including survey programs that will soon discover countless interesting objects needing follow-up observations. Clearly the field is ripe with opportunities for amateurs, professionals, and educators to collaborate. Amateurs will benefit from mentoring by expert professionals, pros will benefit from observations and data processing by increasingly knowledgeable amateurs, and educators will benefit from a larger pool of skilled talent to help them carry out astronomy-education initiatives. We will look at some successful pro-am collaborations that have already borne fruit and examine areas where the need and/or potential for new partnerships is especially large. In keeping with the theme of this special session, we will focus on how pro-am collaborations in astronomy can contribute to science education both inside and outside the classroom, not only for students of school age but also for adults who may not have enjoyed particularly good science education when they were younger. Because nighttime observations with sophisticated equipment are not always possible in formal educational settings, we will also mention other types of pro-am partnerships, including those involving remote observing, data mining, and/or distributed computing.

  10. The utility of Pro Forma Income Statements.

    PubMed

    Reiboldt, Max; Reiboldt, John

    2002-01-01

    Recent headlines surrounding the financial demise of the nation's seventh largest company, Enron, and its subsequent entanglements with its accounting and consulting firm, Arthur Andersen, have placed a cloud of suspicion upon many reasonable business practices that otherwise are considered standard procedure. The proforma income statement is one of those practices. An oft-used tool in financial management, pro formas play a useful role for projecting financial performance based on predictable forecasts or assumptions. Regardless of the current scrutiny, there is still a valid use for accurately prepared statements.

  11. 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