Atrial fibrillation after thoracic surgery for lung cancer: use of a single cut-off value of N-terminal pro-B type natriuretic peptide to identify patients at risk

Postoperative atrial fibrillation (AF) is a well-known complication occurring after thoracic surgery. B-type natriuretic peptide has recently been investigated as a predictive marker of postoperative AF after cardiac surgery. The aim of this study was to evaluate a definite cut-off for N-terminal pro-B type natriuretic peptide (NT-proBNP) in predicting postoperative AF in lung cancer patients. NT-proBNP was determined before and after surgery in 400 patients. Cardiac function was monitored by continuous postoperative ECG and clinical cardiological evaluation. AF occurred in 18% of the patients. Receiver operating characteristic curve analyses identified a cut-off of 182.3?ng l^?1 as the one with the highest sensitivity and specificity. Perioperative increased levels of NT-proBNP seem to predict postoperative AF in patients undergoing thoracic surgery, and a single cut-off of 182.3?ng l^?1 can be used to select high-risk patients who could receive preventive therapy, leading to a considerable decrease in the total costs associated with the management of this complication.     

Plasma intact fibroblast growth factor 23 levels in women with bulimia nervosa: A cross-sectional pilot study

Fibroblast growth factor (FGF) 23, a circulating 26-kDa peptide produced by osteogenic cells, is a novel phosphaturic factor. In our previous study, binge-eating/purging type anorexia nervosa (AN-BP) patients had elevated plasma intact FGF23 (iFGF23) levels, while restricting type (AN-R) patients had plasma iFGF23 levels similar to healthy controls. Although bulimia nervosa (BN) patients as well as some patients with AN-BP regularly engage in binge eating, there have been no studies regarding plasma iFGF23 levels in BN patients. Therefore, this study was performed to determine plasma iFGF23 concentrations in BN patients and healthy controls. The study population consisted of 13 female BN patients and 11 healthy female controls. Blood samples were collected from all subjects after overnight fasting. Plasma iFGF23 was measured using an ELISA kit in a cross-sectional manner. The two-tailed Mann-Whitney U-test was used to assess differences between BN patients and healthy controls. In addition, BN patients were divided into two groups based on questionnaire-reported binge eating frequency immediately prior to participation in this study: high frequency of binge eating (once a week or more; HF group; n = 8) and low frequency of binge eating (less than once a week; LF group; n = 5). Two-tailed Mann-Whitney U-test with Bonferroni's correction was performed after the Kruskal-Wallis test to assess differences between HF group, LF group, and healthy controls. Median (quartiles) plasma iFGF23 levels were greater in BN patients (35.5 [14.8-65.0] pg/ml) than in controls (3.8 [not detected-5.3] pg/ml; p = 0.002). In addition, median (quartiles) plasma iFGF23 levels were greater in the HF group (62.3 [44.4-73.4] pg/ml) than in controls (p < 0.001) and in the LF group (12.9 [not detected-30.3] pg/ml; p = 0.011), while there were no differences between the LF group and controls (p = 0.441). This is the first study to show that BN patients have elevated plasma iFGF23 levels. Moreover, this study showed that BN patients with a high frequency of binge eating have elevated plasma iFGF23 levels, while iFGF23 levels are similar to healthy controls in those with a low frequency of binge eating. Plasma iFGF23 level may be a suitable indicator of binge eating in BN patients.     

Miniaturization and validation of a high-throughput serine kinase assay using the AlphaScreen platform

Reducing costs while maintaining the highest readout quality is a precept of modern high-throughput screening. Given the trend toward nonradiometric screening platforms, this has been a big challenge for some kinase target classes. Common issues include low sensitivity, susceptibility to nonspecific interference, or the need for costly reagents. In this study, the authors describe the feasibility of miniaturization of a serine kinase assay using generic reagents in the AlphaScreen format. They have validated the robustness of this assay in the course of miniaturization from a 35-to 4.375-microL final assay volume in 384-and 1536-well formats. Within this volume range, they consistently obtained Z' values above 0.5 and have investigated the suitability of these assay formats for measuring compound effects by testing a set of 25 previously identified active compounds. These active compounds were also reliably identified in the miniaturized assay formats. The results presented here show that the AlphaScreen technology permits robust and cost-efficient miniaturization of serine/threonine kinase assays.     

Interconnections of fibroblast growth factor 23 and klotho with erythropoietin and hypoxia-inducible factor

Molecular and Cellular Biochemistry - Bone marrow (BM) hematopoiesis is tightly regulated process and bone components such as osteoblasts, extracellular matrix, and minerals influence hematopoiesis...     

Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4 h PO as independent predictors of LCOS, while cTnI 4 h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB.     

Brain-derived fibroblast growth factor: A study of its inactivation

Brain fibroblast growth factor has been identified as a component of myelin basic protein. Its activity is destroyed when treated with a variety of solvents including dilute acid, organic solvents and solutions of guanidine hydrochloride. These conditions do not alter the encephalitogenic properties of myelin basic protein.     

Detection of oxytocin,atrial natriuretic peptide,and brain natriuretic peptide using novel imprinted polymers produced with amphiphilic monomers

The cystine‐bridged cyclic peptide hormones (CBCPHs) represent signature structural feature as well as unique biological activity. In this study, three CBCPHs have been identified and characterized, namely, oxytocin, atrial natriuretic peptides (ANPs), and brain natriuretic peptides (BNPs). Because research has shown that ANPs and BNPs are powerful diagnostic biomarkers for heart disease, a highly laudable endeavor would be to develop a novel sensor for detecting ANP or BNP levels. Therefore, an amphiphilic monomer Acr‐His‐NHNH‐Fmoc was synthesized to form molecularly imprinted polymers (MIPs) for targeted CBCPH detection. First, oxytocin, a cardiovascular hormone and a CBCPH, was used as a template to fabricate MIPs on quartz crystal microbalance (QCM) chips. On the other hand, fabricated selected ANP segment or BNP segment as an epitope is able to construct epitope‐mediated MIPs (EMIPs) for ANP or BNP. The developed oxytocin or ANP sensor reached a detection limitation of 0.1nM with the dissociation constants being 30pM for oxytocin and 20pM for ANP. Moreover, BNP sensor achieved a detection limitation of 2.89pM with an even lower K_d value as 2pM. Compared with the performance of EMIPs, the imprinted films showed high affinity and selectivity in special binding to CBCPHs. The developed MIPs‐QCM biosensors thus provide an improved sensing platform using an amphiphilic monomer and may be useful for applications toward cyclotides, cystine knot motifs, or insulin‐like peptides.     

A possible contribution of endogenous atrial natriuretic peptide to proteinuria in patients with chronic renal failure.

Plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured with a specific radioimmunoassay in 19 undialysed patients with chronic renal failure. At the beginning, an extremely high level of plasma hANP (50 fmol/ml) seen in a patient was rejected with Smirnov's test and was excluded from further statistics. The plasma IR-ANP levels in these patients were significantly higher than those of 19 normal subjects matched with age and sex (10.9 +/- 1.6 vs 5.3 +/- 0.6 fmol/ml, mean +/- SEM, p less than 0.01), and positively correlated with mean blood pressure (r = 0.44, p less than 0.05) and the cardiothoracic ratio (r = 0.65, p less than 0.01), but did not correlate with creatinine clearance (r = -0.38, n.s.). Further, a significant correlation was observed between plasma IR-ANP and urinary protein output (r = 0.47, p less than 0.05). On the other hand, urinary protein output did not correlate significantly with variables such as mean blood pressure, the cardiothoracic ratio or creatinine clearance. Since it has been suggested that ANP enhances glomerular capillary permeability, increased ANP responding to volume overload in those patients may play an important role in increasing urinary protein excretion.     

B-type natriuretic peptide in children with atrial or ventricular septal defect: a cardiac catheterization study

In this study, we investigated the relationship between plasma B-type natriuretic peptide (BNP) levels and hemodynamics from cardiac catheterization in pediatric patients with atrial or ventricular septal defect. A total of 59 patients were studied including 80% of patients had Qp/Qs > 1.5 and 25% of patients had pulmonary hypertension. The mean BNP value and BNP z-score were 10.9?±?11.2 pg/mL and ?0.28?±?1.7 (?2.85 to 3.29), respectively. There was a statistically significant linear correlation between BNP value and the size of defects (r?=?0.303, p?=?0.002) and a trend toward to positive correlation between BNP value and Qp/Qs ratio (r?=?0.183, p?=?0.166) among all patients. To identify patients with a Qp/Qs ratio >1.5, the sensitivity and specificity were 28%, 100% in all patients at a plasma BNP cut-off point of 15 pg/mL. We concluded that a BNP > 15 pg/mL would help identify patients who need further intervention.     

B-type natriuretic peptide in children with atrial or ventricular septal defect: a cardiac catheterization study

In this study, we investigated the relationship between plasma B-type natriuretic peptide (BNP) levels and hemodynamics from cardiac catheterization in pediatric patients with atrial or ventricular septal defect. A total of 59 patients were studied including 80% of patients had Qp/Qs > 1.5 and 25% of patients had pulmonary hypertension. The mean BNP value and BNP z-score were 10.9?±?11.2 pg/mL and -0.28?±?1.7 (-2.85 to 3.29), respectively. There was a statistically significant linear correlation between BNP value and the size of defects (r?=?0.303, p?=?0.002) and a trend toward to positive correlation between BNP value and Qp/Qs ratio (r?=?0.183, p?=?0.166) among all patients. To identify patients with a Qp/Qs ratio >1.5, the sensitivity and specificity were 28%, 100% in all patients at a plasma BNP cut-off point of 15 pg/mL. We concluded that a BNP > 15 pg/mL would help identify patients who need further intervention.     

Serum level of transforming growth factor beta 1 is associated with left atrial voltage in patients with chronic atrial fibrillation

Background

Atrial tissue fibrosis can cause electrical or structural remodeling in patients with atrial fibrillation. Transforming growth factor beta 1(TGF-β1) signaling acts as a central role in fibroblast activation. In this report, we aimed to investigate the relationship between serum level of TGF-β1 and mean left atrial voltage in patients with chronic atrial fibrillation (CAF).

Increased secretion of brain natriuretic peptide and atrial natriuretic peptide, but not sufficient to induce natriuresis in rats with nephrotic syndrome.

The levels of immunoreactive brain natriuretic peptide (ir-BNP) and immunoreactive atrial natriuretic peptide (ir-ANP) were evaluated by radioimmunoassay in both the atrium, ventricle and plasma of adriamycin-induced nephrotic rats and control rats. There was no difference in right and left atrial concentrations of ir-BNP, however, a higher right atrial concentration of ir-ANP was observed in nephrotic rats than in controls (p less than 0.01). The ventricular ir-BNP and ir-ANP were increased in nephrotic rats compared to controls (BNP: p less than 0.001, ANP: p less than 0.001). Cardiac BNPs were composed of pro-BNP (gamma-BNP) and its C-terminal 45-amino-acid peptide (BNP-45). The ratio of BNP-45/gamma-BNP in nephrotic rats was higher than that of controls in both atria and in the ventricle. Plasma ir-BNP and ir-ANP were significantly higher in nephrotic rats than in controls (BNP: p less than 0.001, ANP: p less than 0.001), and each level was negatively correlated with urinary sodium excretion in nephrotic rats (BNP: r = -0.84, p less than 0.001, ANP: r = -0.88, p less than 0.001). These results suggest that production and secretion of both BNP and ANP are concomitantly stimulated by a decreased renal ability to eliminate sodium and water, but this secretion is insufficient to induce effective natriuresis in nephrotic rats.     

Effects of atrial natriuretic peptide infusion and its metabolism in patients with chronic renal failure.

Synthetic alpha-human atrial natriuretic peptide (hANP) was infused continuously at a rate of 80 ng/kg/min for 20 min into normal volunteers and patients with chronic renal failure (CRF) receiving hemodialysis. Blood pressure (BP) decreased significantly both in normals and in patients with CRF. The magnitude and the duration of the decrease, however, were greater in patients with CRF. The plasma aldosterone concentration (PAC) decreased significantly in normals and only minimally in patients with CRF. The half time (T1/2) of plasma hANP in patients with CRF (M +/- SE: 4.5 +/- 0.5 min) was longer than that in normals (1.8 +/- 0.2 min). Moreover, the metabolic clearance rate in patients with CRF (64 +/- 7 ml/kg/min) was less than in normals (150 +/- 20 ml/kg/min). Thus, the T1/2 in plasma of hANP in patients with CRF was noticeably longer than in a normal control group. These findings suggest that hANP suppresses PAC regardless of electrocyte imbalances and/or volume change induced by kidney dysfunction and that the kidney may be important in degrading hANP.     

Preoperative levels of natriuretic peptides and the incidence of postoperative atrial fibrillation after noncardiac surgery: a prospective cohort study

BACKGROUND:Postoperative atrial fibrillation (POAF) is associated with clinically significant short- and long-term complications after noncardiac surgery. Our aim was to describe the incidence of clinically important POAF after noncardiac surgery and establish the prognostic value of N-terminal pro–brain-type natriuretic peptide (NT-proBNP) in this context.METHODS:The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Study was a prospective cohort study involving patients aged 45 years and older who had inpatient noncardiac surgery that was performed between August 2007 and November 2013. We determined 30-day incidence of clinically important POAF (i.e., resulting in angina, congestive heart failure, symptomatic hypotension or requiring treatment) using logistic regression models to analyze the association between preoperative NT-proBNP and POAF.RESULTS:In 37 664 patients with no history of atrial fibrillation, we found that the incidence of POAF was 1.0% (95% confidence interval [CI] 0.9%–1.1%; 369 events); 3.2% (95% CI 2.3%–4.4%) in patients undergoing major thoracic surgery, 1.3% (95% CI 1.2%–1.5%) in patients undergoing major nonthoracic surgery and 0.2% (95% CI 0.1%–0.3%) in patients undergoing low-risk surgery. In a subgroup of 9789 patients with preoperative NT-proBNP measurements, the biomarker improved the prediction of POAF risk over conventional prognostic factors (likelihood ratio test p < 0.001; fraction of new information from NT-proBNP was 16%). Compared with a reference NT-proBNP measurement set at 100 ng/L, adjusted odds ratios for the occurrence of POAF were 1.31 (95% CI 1.15–1.49) at 200 ng/L, 2.07 (95% CI 1.27–3.36) at 1500 ng/L and 2.39 (95% CI 1.26–4.51) at 3000 ng/L.INTERPRETATION:We determined that the incidence of clinically important POAF after noncardiac surgery was 1.0%. We also found that preoperative NT-proBNP levels were associated with POAF independent of established prognostic factors. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT00512109","term_id":"NCT00512109"}}NCT00512109

Postoperative atrial fibrillation (POAF) is the most common arrhythmia that occurs after noncardiac surgery¹ and is associated with prolonged hospital stays and an increased risk of stroke and death,^2–8 both of which raise societal costs.⁹ The reported incidence of POAF ranges from 3.7% to 21.0% in patients undergoing thoracic surgery^3,10 and from less than 0.5% to 10.0% in patients undergoing noncardiac, nonthoracic surgery (Appendix 1, Supplementary Table 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.200840/tab-related-content).^6,11Brain-type natriuretic peptide (BNP) is a neurohormone released by cardiomyocytes in response to volume and pressure overload.¹² This biomarker has an established role in the diagnosis and management of heart failure and in predicting cardiovascular morbidity and mortality.¹³ Although natriuretic peptides have been shown to predict new-onset atrial fibrillation (AF) in the nonsurgical setting reliably,^14–18 their value in predicting POAF after noncardiac surgery is unclear.^19–21The Vascular events In non-cardiac Surgery patIents cOhort evaluatioN (VISION) Study was a prospective international cohort study involving a representative sample of adults who underwent noncardiac surgery that required an overnight hospital stay. One of the predefined objectives in VISION was to determine the incidence of new-onset, clinically important POAF. We aimed to describe the overall and surgery-specific incidence of POAF after noncardiac surgery and to investigate the association between preoperative N-terminal pro–brain-type natriuretic peptide (NT-proBNP) and POAF. We hypothesized that measurement of NT-proBNP would improve POAF risk prediction beyond conventional prognostic factors.     

Plasma levels of adrenomedullin and atrial natriuretic peptide in patients with congestive heart failure of various etiologies

OBJECTIVE: The aim of this study was to evaluate the plasma levels of the adrenomedullin (ADM) and atrial natriuretic peptide (ANP) in adult and pediatric patients with congestive heart failure (CHF) of various etiologies and to investigate their relations with haemodynamic variables e.g. echocardiographic left ventricular ejection fraction (LVEF) and fractional shortening (FS). SUBJECTS AND METHODS: The study was made in 38 adult and 21 pediatric patients with CHF of various etiologies and compared with 15 adult and 10 pediatric normal healthy controls. Patients with CHF were classified according to the New York Heart Association (NYHA) functional classification into grades II to IV in adult patients and into grade IV in all pediatric patients. ADM and ANP plasma levels were determined prior to the treatment with enzyme immunoassay. RESULTS: A statistically significant difference in the plasma levels of ADM and ANP were found between pediatrics and adult patients and corresponding healthy controls. Their levels were progressively increased with severity of NYHA class in adult patients. We found a significant positive correlation between plasma levels of each of ADM and ANP and pulse rate, systolic and diastolic blood pressure; and a significant negative correlation between their plasma levels and echocardiographic LVEF and FS. A significant positive correlation between plasma levels of ADM and ANP in both pediatrics and adult patients were also found. CONCLUSION: Plasma levels of ADM and ANP increased in adult and pediatric patients with CHF irrespective of the cause. They were positively correlated with each other and negatively correlated with LVEF and FS. These findings might have important clinical implications in that a noninvasive blood test may be used to identify high-risk subjects for HF for more invasive procedures.     

Developmental origins of pregnancy-induced cardiac changes: establishment of a novel model using the atrial natriuretic peptide gene-disrupted mice

Molecular and Cellular Biochemistry - Pregnancy evokes many challenges on the maternal cardiovascular system that may unmask predispositions for future disease. This is particularly evident for...     

Effects of serum, fibroblast growth factor, and platelet-derived growth factor on explants of rat tail tendon: a morphological study

Eighteen tail tendon fascicles were explanted from a 40-day postpartum rat and maintained in both serum-supplemented and serum-free Eagle's minimal essential medium for 2 weeks. Epitendon and paratendon connective tissues were excluded from these explants. Tendon fibroblasts maintained in serum-supplemented medium proliferated and synthesized collagen. Tendon fibroblasts explanted in serum-free medium remained viable but did not proliferate. Fibroblast growth factor and platelet-derived growth factor were shown to stimulate proliferation of mature tendon fibroblasts in serum-free medium.