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Peptide Levels (peptide + level)
Kinds of Peptide Levels Selected AbstractsUsefulness of Brain Natriuretic Peptide Level at Implant in Predicting Mortality in Patients with Advanced But Stable Heart Failure Receiving Cardiac Resynchronization TherapyCLINICAL CARDIOLOGY, Issue 11 2009Aiman El-Saed MD Abstract Background Brain natriuretic peptide (BNP) level has emerged as a predictor of death and hospital readmission in patients with heart failure (HF). The value of baseline BNP assessment in advanced HF patients receiving cardiac resynchronization defibrillator therapy (CRT-D) has not been firmly established. Hypothesis We hypothesized that a baseline BNP level would predict all cause mortality and HF hospitalization in HF patients receiving cardiac resynchronization therapy. Methods A retrospective chart review of all patients having BNP assessment prior to implantation of a CRT-D for standard indications during 2004 and 2005 was conducted at the Veterans Affairs Pittsburgh Healthcare System. The primary endpoint was all-cause mortality and the secondary endpoint was HF-related hospitalization. We used findings from the receiver operating characteristic (ROC) curve to define low (<492 pg/mL) and high (,492 pg/mL) BNP groups. Results Out of 173 CRT-D recipients, 115 patients (mean age 67.0 ± 10.7 years, New York Heart Association [NYHA] class 2.9 ± 0.3, left ventricular ejection fraction [LVEF] 22.5% ± 9.6%, QRS 148.3 ± 30.4 ms) had preimplantation BNP measured (mean 559 ± 761 pg/mL and median 315 pg/mL). During a mean follow-up time of 17.5 ± 6.5 mo, 27 deaths (23.5%) and 31 HF hospitalizations (27.0%) were recorded. Compared to those with low BNP (n = 74), those of high BNP (n = 41) were older, had lower LVEF, higher creatinine levels, suffered more deaths, and HF hospitalizations. In multivariate regression models, higher BNP remained a significant predictor of both the primary endpoint (hazard ratio [HR]: 2.89, 95% confidence interval [CI] 1.06,7.88, p = 0.038) and secondary endpoint (HR: 4.23, 95% CI: 1.68,10.60, p = 0.002). Conclusions Baseline BNP independently predicted mortality and HF hospitalization in a predominantly older white male population of advanced HF patients receiving CRT-D. Elevated BNP levels may identify a vulnerable HF population with a particularly poor prognosis despite CRT-D. Copyright © 2009 Wiley Periodicals, Inc. [source] Brain Natriuretic Peptide Levels and Response to Cardiac Resynchronization Therapy in Heart Failure PatientsCONGESTIVE HEART FAILURE, Issue 5 2006Reynolds M. Delgado MD The authors used brain natriuretic peptide (BNP) as a reliable marker to identify nonresponders to cardiac resynchronization therapy (CRT) in patients with advanced heart failure. The study included 70 patients with left ventricular dysfunction (mean ejection fraction, 21±4%) and left bundle branch block (QRS duration, 164±25 milliseconds) treated with CRT. The authors reviewed data on New York Heart Association functional class, baseline ejection fraction, sodium, creatinine, QRS duration, and BNP levels 3 months before and after CRT therapy. The authors compared results of 42 patients who survived (973+192 days) after CRT implantation (responders) to those of 28 patients (nonresponders) who either expired (n=21) or underwent heart transplantation (n=5) or left ventricular assist device implantation (n=2) after an average of 371+220 days. Mean BNP levels after 3 months of CRT decreased in responders from 758±611 pg/mLto 479±451 pg/mL (P=.044), while in nonresponders there was increase in BNP levels from 1191 ±466 pg/mL to 1611 ±1583; P=.046. A rise in BNP levels was associated with poor response (death or need for transplantation or left ventricular assist device and impaired long-term outcome), which makes it a good predictor to identify such patients. [source] Combination of B-Type Natriuretic Peptide Levels and Non-Invasive Hemodynamic Parameters in Diagnosing Congestive Heart Failure in the Emergency DepartmentCONGESTIVE HEART FAILURE, Issue 4 2004Erin Barcarse BS This study aimed to assess whether the combination of a B-type natriuretic peptide (BNP) level with various noninvasive hemodynamic parameters can help physicians more quickly and accurately diagnose congestive heart failure and determine the type of left ventricular dysfunction present in patients presenting to the emergency department with dyspnea. Subjects were 98 men (aged 64.57±1.23 years) that presented to the VA San Diego Healthcare System. Hemodynamic parameters were measured using impedance cardiography, and BNP levels were quantified using a rapid immunoassay. All patients with a BNP <100 pg/mL (n=37) had no evidence of congestive heart failure 97% of the time. In those with a BNP >100 pg/mL (601 ±55 pg/mL; n=61), a cardiac index of 2.6 L/min/m2 is 65% sensitive and 88% specific in determining systolic dysfunction. In patients with a BNP >100 pg/mL, a multivariate model consisting of noninvasive hemodynamic measurements was able to predict cardiac deaths, readmissions, and emergency department visits within 90 days with 83% accuracy. The authors conclude that, in patients presenting to an emergency department with dyspnea, the addition of impedance cardiography measurements to BNP level measurements will more effectively diagnose congestive heart failure and determine both the type of heart dysfunction and the severity of illness. [source] The Effect of Beta-Blocker (Carvedilol) Therapy on N-Terminal Pro-Brain Natriuretic Peptide Levels and Echocardiographic Findings in Patients with Congestive Heart FailureECHOCARDIOGRAPHY, Issue 2 2007Fuat Gundogdu M.D. Background: The favorable effects of beta-blockers on decreasing mortality in contemporary heart failure management have been demonstrated in recent years. N-terminal pro-brain natriuretic (NT-proBNP) peptide levels increase in patients with heart failure. The purpose of this study was to investigate the correlation between the NT-proBNP levels and echocardiographic findings for the patients who received carvedilol therapy in addition to standard therapy for congestive heart failure. Methods and Results: A total of 25 patients with symptomatic congestive heart failure and 25 healthy individuals were enrolled in the study. Before introducing beta-blocker into their therapy regimens, baseline transthoracic echocardiography recordings were made and venous blood samples were drawn for establishing NT-proBNP levels. The patients were administered with a minimum dose of carvedilol. Three months after reaching the maximum tolerable dose, blood samples were drawn from the patients once again for NT-proBNP measurements, and transthoracic echocardiography was performed. There was a significant drop in plasma NT-proBNP levels at the end of the study in comparison to the baseline values (baseline: 381.20±35.06 pg/mL, at the end of the third month: 254.44±28.64 pg/mL; P < 0.001). While left ventricular end-diastolic and end-systolic diameters were observed to have significantly decreased as a result of the therapy (P < 0.001), left ventricular ejection fraction (P<0.001) was established to have increased significantly. Conclusions: Carvedilol therapy resulted in a marked decrease in plasma NT-proBNP levels and increase left ventricular ejection fraction in patients with congestive heart failure. [source] Performance of Phonoelectrocardiographic Left Ventricular Systolic Time Intervals and B-Type Natriuretic Peptide Levels in the Diagnosis of Left Ventricular DysfunctionANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2007Brian Moyers M.D. Background: Systolic time intervals measured by echocardiography and carotid artery tracings are validated methods of assessing left ventricular function. However, the clinical utility of phonoelectrocardiographic systolic time intervals for predicting heart failure using newer technology has not been evaluated. Methods: We enrolled 100 adult patients undergoing left heart catheterization. Participants underwent computerized phonoelectrocardiographic analysis, left ventricular end-diastolic pressure (LVEDP) measurement, transthoracic echocardiographic measurement of left ventricular ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. The heart rate-adjusted systolic time intervals included the time from the Q wave onset to peak S1 (electromechanical activation time, EMAT), Q wave onset to peak S2 (electromechanical systole, Q-S2), and peak S1 to peak S2 (left ventricular systolic time, LVST). Left ventricular dysfunction was defined as the presence of both LVEDP >15 mmHg and LVEF <50%. Results: EMAT (r =,0.51; P < 0.0001), EMAT/LVST (r =,0.41; P = 0.0001), and Q-S2 (r =,0.39; P = 0.0003) correlated with LVEF, but not with LVEDP. An abnormal EMAT ,15 (odds ratio 1.38, P < 0.0001) and EMAT/LVST ,0.40 (OR 1.13, P = 0.002) were associated with left ventricular dysfunction. EMAT ,15 had 44% sensitivity, 94% specificity, and a 7.0 likelihood ratio for left ventricular dysfunction, while EMAT/LVST ,0.40 had 55% sensitivity, 95% specificity, and a 11.7 likelihood ratio. In patients with an intermediate BNP (100,500 pg/mL), the likelihood ratio increased from 1.1 using the BNP result alone to 11.0 when adding a positive EMAT test for predicting left ventricular dysfunction. Conclusions: Phonoelectrocardiographic measures of systolic time intervals are insensitive but highly specific tests for detecting abnormalities in objective markers of left ventricular function. EMAT and EMAT/LVST provide diagnostic information independent of BNP for detecting patients with left ventricular dysfunction. [source] The Influence of Left Ventricle Diastolic Function on Natriuretic Peptides Levels in Patients with Atrial FibrillationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2009DAWID BAKOWSKI M.D., Ph.D. Background:The diagnosis of the impaired left ventricle (LV) diastolic function during atrial fibrillation (AF) using traditional methods is very difficult. Natriuretic peptides seem to be useful for assessment of diastolic function in patients with AF. Aim:To evaluate the influence of LV diastolic dysfunction on natriuretic peptides concentrations and to assess the diagnostic value of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with AF and impaired LV diastolic function. Methods:The study included 42 patients (23 males, 19 females), aged 58.6 ± 8.2 years with nonvalvular persistent AF with preserved LV systolic function who were converted into sinus rhythm by DC cardioversion (CV) and maintained sinus rhythm for at least 30 days. Echocardiography (ECG), ANP, and BNP level measurements were taken at baseline 24 hours before CV and 24 hours and 30 days after CV. On the 30th day following CV in patients with sinus rhythm, Doppler ECG was performed to assess LV diastolic function. Results:Thirty days after CV, normal LV diastolic function in 15 patients and impaired diastolic function in 27 patients was diagnosed: 20 with impaired LV relaxation and seven with impaired LV compliance. During AF and 24 hours, and 30 days after sinus rhythm restoration, significantly higher ANP and BNP levels were observed in patients with LV diastolic dysfunction as compared to the subgroup with normal LV diastolic function. The average values of ANP during AF in patients with normal and impaired diastolic function were 167.3 ± 70.1 pg/mL and 298.7 ± 83.6 pg/mL, respectively (P < 0.001), and the average values of BNP in the above mentioned subgroups were 49.5 ± 14.7 pg/mL and 145.6 ± 49.6 pg/mL respectively (P < 0.001). While comparing the diagnostic value of both natriuretic peptides it was noted that BNP was a more specific and sensitive marker of impaired LV diastolic function. ANP value >220.7 pg/mL measured during AF identified patients with impaired LV diastolic function with 85% sensitivity and 90% specificity. BNP value >74.7 pg/mL proved 95% sensitive and 100% specific in the diagnosing of such a group. Conclusions:The increase of ANP/BNP concentration in patients with AF results not only from the presence of AF, but also reflects the impaired LV diastolic function. Natriuretic peptides, especially BNP, may be useful in diagnosing LV diastolic dysfunction in patients with AF. [source] Effect of Bisoprolol on Right Ventricular Function and Brain Natriuretic Peptide in Patients With Heart FailureCONGESTIVE HEART FAILURE, Issue 3 2004Luís Beck-da-Silva MD Beta-blocker use improves left ventricular ejection fraction (LVEF) in patients with heart failure. A similar effect of , blockers on right ventricular function has been proposed, although the effect of bisoprolol, a highly selective ,-1 blocker, on right ventricular function has not been assessed. This study investigated the short-term effect of bisoprolol on right ventricular function in chronic heart failure patients. A cohort of 30 heart failure patients who were not taking , blockers at baseline was studied prospectively. Right ventricular ejection fraction (RVEF) and LVEF were measured at both baseline and 4 months by radionuclide angiography. Bisoprolol was up-titrated during four monthly visits by a preestablished protocol to a target dose of 10 mg/d. The dose of vasodilators was not changed. Quality of life and brain natriuretic peptide level were assessed. Mean age was 62.7±14.3 years. Baseline RVEF was 30.7%±6.3% and baseline LVEF was 21.7%±9.4%. Mean bisoprolol dose reached was 5.3±3.9 mg daily. At 4 months, RVEF significantly increased by 7.1 % (95% confidence interval, 3.9,10.2; p=0.0001) and LVEF also increased significantly by 7.9% (95% confidence interval, 4.0%,11.9%p=0.0003). Quality-of-life score improved from 42.8 to 30.8 (p=0.047). No correlation was found between brain natriuretic peptide levels and RVEF. Bisoprolol treatment for 4 months resulted in a significant improvement of RVEF, which paralleled the improvement of LVEF. [source] Correlation between NT-pro BNP Levels and Early Mitral Annulus Velocity (E,) in Patients with Non,ST-Segment Elevation Acute Coronary SyndromeECHOCARDIOGRAPHY, Issue 4 2008Marcia M. Barbosa M.D., Ph.D. Acute coronary syndromes in the absence of ST-segment elevation (NSTE-ACS) are a heterogeneous entity in which early risk stratification is essential. Diastolic dysfunction is precocious and associated with poor prognosis. BNP has been recognized as a biochemical marker of ventricular dysfunction and ischemia. Objective: To investigate if there is correlation of NT pro-BNP levels with diastolic dysfunction in patients with NSTE-ACS. Methods: Fifty-two patients with NSTE-ACS admitted to the coronary unit were included. NT-pro brain natriuretic hormone (BNP) levels and a Doppler echocardiogram were obtained in all and systolic and diastolic functions were analyzed. Their Doppler indexes were compared with those of 53 age- and sex-matched controls, without heart failure symptoms and with normal ejection fraction (EF) and normal NT-pro BNP levels. Results: Twenty-four patients (46%) with unstable angina and 28 patients (54%) with acute myocardial infarction (AMI) were included. Mean EF was 55.9 ± 10.7% and mean NT-pro BNP level was 835 ± 989 pg/ml. No mitral or pulmonary venous flow parameters of diastolic function correlated with NT-pro BNP levels. E,/A, correlated with NT-pro BNP level in univariate analysis but, in a multivariate analysis, only the EF and the E, showed negative correlation with the peptide level (r =,0.33, P = 0.024 and r =,0.29, P = 0.045, respectively). Thirteen patients presented with stage II diastolic dysfunction but the NT-pro BNP level in these patients did not differ from the level in stage I patients. Conclusion: NT-pro BNP levels are elevated in acute coronary syndromes, even in the absence of significant necrosis. Of all echocardiographic parameters investigated, only E, and the EF correlated with the levels of NT-pro BNP in this group of patients. [source] Hospitalized patients with acute decompensated heart failure: Recognition, risk stratification, and treatment reviewJOURNAL OF HOSPITAL MEDICINE, Issue S6 2008Alpesh Amin MD Abstract Acute decompensated heart failure (ADHF) has emerged as a major healthcare problem. It causes approximately 3% of all hospitalizations in the United States, with the direct medical cost of these hospitalizations estimated at $18.8 billion per year. Early recognition, risk stratification, and evidence-based treatment are crucial in reducing the morbidity, mortality, and costs associated with this disorder. Classic signs and symptoms of ADHF, such as rales, dyspnea, and peripheral edema, may be absent at hospital presentation and, even when present, are not specific to this disorder. As a result, serum B,type natriuretic peptide level is now used to rapidly and accurately detect ADHF. Multivariate analyses have identified renal dysfunction, hypotension, advanced age, hyponatremia, and comorbidities as significant and independent mortality risk factors. Based on these factors, mortality risk can be stratified from very low to very high using published algorithms that have been validated in independent populations. Evidence-based guidelines for the treatment of ADHF are available from both the European Society of Cardiology and the Heart Failure Society of America. In general, an intravenous loop diuretic, either alone or in combination with a vasodilator, is recommended as initial therapy in patients with volume overload, depending on the patient's clinical status. Use of inotropic agents should be limited to the small subset of patients with low-output syndrome and significant hypotension. In any event, frequent monitoring of clinical response is essential, with subsequent therapy determined by this response. Finally, focused patient education during hospitalization may help reduce readmissions for ADHF. Journal of Hospital Medicine 2008;3(Suppl 6):S16,S24. © 2008 Society of Hospital Medicine. [source] Proteomics by FTICR mass spectrometry: Top down and bottom upMASS SPECTROMETRY REVIEWS, Issue 2 2005Bogdan Bogdanov Abstract This review provides a broad overview of recent Fourier transform ion cyclotron resonance (FTICR) applications and technological developments relevant to the field of proteomics. Both the "bottom up" (peptide level) and "top down" (intact protein level) approaches are discussed and illustrated with examples. "Bottom up" topics include peptide fragmentation, the accurate mass and time (AMT) tag approach and dynamic range extension technology, aspects of quantitative proteomics measurements, post-translational modifications, and developments in FTICR operation software focused on peptide and protein identification. Topics related to the "top down" approach include various aspects of high mass measurements, protein tandem mass spectrometry, methods for the study of protein conformations, and protein complexes as well as advanced technologies that may become of practical utility in the coming years. Finally, early examples of the integration of both FTICR approaches to biomedical proteomics applications are presented, along with an outlook for future directions. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:168,200, 2005 [source] Brain natriuretic peptide level as marker of cardiac function in imatinib,Treated chronic myeloid leukemia patients: No evidence of cardiotoxicity of imatinib therapyAMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2008Mario Tiribelli No abstract is available for this article. [source] Comparison of alternative analytical techniques for the characterisation of the human serum proteome in HUPO Plasma Proteome ProjectPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 13 2005Xiaohai Li Abstract Based on the same HUPO reference specimen (C1-serum) with the six proteins of highest abundance depleted by immunoaffinity chromatography, we have compared five proteomics approaches, which were (1) intact protein fractionation by anion-exchange chromatography followed by 2-DE-MALDI-TOF-MS/MS for protein identification (2-DE strategy); (2) intact protein fractionation by 2-D HPLC followed by tryptic digestion of each fraction and microcapillary RP-HPLC/microESI-MS/MS identification (protein 2-D HPLC fractionation strategy); (3) protein digestion followed by automated online microcapillary 2-D HPLC (strong cation-exchange chromatography (SCX)-RPC) with IT microESI-MS/MS; (online shotgun strategy); (4) same as (3) with the SCX step performed offline (offline shotgun strategy) and (5) same as (4) with the SCX fractions reanalysed by optimised nanoRP-HPLC-nanoESI-MS/MS (offline shotgun-nanospray strategy). All five approaches yielded complementary sets of protein identifications. The total number of unique proteins identified by each of these five approaches was (1) 78, (2) 179, (3) 131, (4) 224 and (5) 330 respectively. In all, 560 unique proteins were identified. One hundred and sixty-five proteins were identified through two or more peptides, which could be considered a high-confidence identification. Only 37 proteins were identified by all five approaches. The 2-DE approach yielded more information on the pI -altered isoforms of some serum proteins and the relative abundance of identified proteins. The protein prefractionation strategy slightly improved the capacity to detect proteins of lower abundance. Optimising the separation at the peptide level and improving the detection sensitivity of ESI-MS/MS were more effective than fractionation of intact proteins in increasing the total number of proteins identified. Overall, electrophoresis and chromatography, coupled respectively with MALDI-TOF/TOF-MS and ESI-MS/MS, identified complementary sets of serum proteins. [source] Strategic shotgun proteomics approach for efficient construction of an expression map of targeted protein families in hepatoma cell linesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 12 2003Chih-Lei Lee Abstract An expression map of the most abundant proteins in human hepatoma HepG2 cells was established by a combination of complementary shotgun proteomics approaches. Two-dimensional liquid chromatography (LC)-nano electrospray ionization (ESI) tandem mass spectrometry (MS/MS) as well as one-dimensional LC-matrix-assisted laser desorption/ionization MS/MS were evaluated and shown that additional separation introduced at the peptide level was not as efficient as simple prefractionation of protein extracts in extending the range and total number of proteins identified. Direct LC-nanoESI MS/MS analyses of peptides from total solubilized fraction and the excised gel bands from one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis fractionated insolubilized fraction afforded the best combination in efficient construction of a nonredundant cell map. Compiling data from multiple variations of rapid shotgun proteomics analyses is nonetheless useful to increase sequence coverage and confidence of hits especially for those proteins identified primarily by a single or two peptide matches. While the returned hit score in general reflects the abundance of the respective proteins, it is not a reliable index for differential expression. Using another closely related hepatoma Hep3B as a comparative basis, 16 proteins with more than two-fold difference in expression level as defined by spot intensity in two-dimensional gel electrophoresis analysis were identified which notably include members of the heat shock protein (Hsp) and heterogeneous nuclear ribonucleoprotein (hnRPN) families. The observed higher expression level of hnRNP A2/B1 and Hsp90 in Hep3B led to a search for reported functional roles mediated in concert by both these multifunctional cellular chaperones. In agreement with the proposed model for telomerase and telomere bound proteins in promoting their interactions, data was obtained which demonstrated that the expression proteomics data could be correlated with longer telomeric length in tumorigenic Hep3B. This biological significance constitutes the basis for further delineation of the dynamic interactions and modifications of the two protein families and demonstrated how proteomic and biological investigation could be mutually substantiated in a productive cycle of hypothesis and pattern driven research. [source] Glutamine deamidation of a recombinant monoclonal antibodyRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2008Hongcheng Liu Deamidation of glutamine (Gln) proceeds at a much slower rate than deamidation of asparagine (Asn) residues at peptide level. However, deamidation of Gln residues in native proteins may occur faster because of the impact of protein structure and thus plays a significant role in affecting protein stability. Gln deamidation of a recombinant monoclonal IgG1 antibody was investigated in the current study. Deamidation was determined by a molecular weight increase of 1,Da, a retention time shift on reversed-phase chromatography and tandem mass spectrometric (MS/MS) analysis of the peptides. As expected, Gln residues at different locations in the three-dimensional structure had different susceptibilities to deamidation. Gln deamidation was highly pH dependent with the highest level detected in the sample incubated at pH 9, and lowest level at pH 6 in the pH range from 5 to 9. The detection of significant levels of Gln deamidation suggested that it may play an important role in affecting heterogeneity and stability of recombinant monoclonal antibodies. Copyright © 2008 John Wiley & Sons, Ltd. [source] The Use of B-Type Natriuretic Peptides in the Intensive Care UnitCONGESTIVE HEART FAILURE, Issue 2008Christian Mueller MD B-type natriuretic peptide levels are quantitative markers of cardiac stress and heart failure that summarize the extent of systolic and diastolic left ventricular dysfunction, valvular dysfunction, and right ventricular dysfunction. Initial observational pilot studies have addressed 7 potential indications in the intensive care unit: identification of cardiac dysfunction, diagnosis of hypoxic respiratory failure, risk stratification in severe sepsis and septic shock, evaluation of patients with shock, estimation of invasive measurements, weaning from mechanical ventilation, as well as perioperative and postoperative risk prediction. Although additional studies are required to better define the clinical utility of B-type natriuretic peptide values in the intensive care unit, current data suggest that the diagnosis of hypoxic respiratory failure and timing of extubation seem to be the most promising indications. Congest Heart Fail. 2008;14(4 suppl 1):43,45. ©2008 Le Jacq [source] Brain Natriuretic Peptide and Diastolic Dysfunction in the Elderly: Influence of GenderCONGESTIVE HEART FAILURE, Issue 2 2005Chanwit Roongsritong MD Diastolic heart failure is common in the elderly, particularly women. Previous studies on the value of brain natriuretic peptide in diastolic dysfunction have been largely limited to male subjects. The authors found that female gender, in addition to diastolic function, is an independent predictor of brain natriuretic peptide levels in the elderly without systolic ventricular dysfunction. The authors' data indicate that an optimal threshold of brain natriuretic peptide for detecting diastolic dysfunction should be qender-specific. [source] Effect of Bisoprolol on Right Ventricular Function and Brain Natriuretic Peptide in Patients With Heart FailureCONGESTIVE HEART FAILURE, Issue 3 2004Luís Beck-da-Silva MD Beta-blocker use improves left ventricular ejection fraction (LVEF) in patients with heart failure. A similar effect of , blockers on right ventricular function has been proposed, although the effect of bisoprolol, a highly selective ,-1 blocker, on right ventricular function has not been assessed. This study investigated the short-term effect of bisoprolol on right ventricular function in chronic heart failure patients. A cohort of 30 heart failure patients who were not taking , blockers at baseline was studied prospectively. Right ventricular ejection fraction (RVEF) and LVEF were measured at both baseline and 4 months by radionuclide angiography. Bisoprolol was up-titrated during four monthly visits by a preestablished protocol to a target dose of 10 mg/d. The dose of vasodilators was not changed. Quality of life and brain natriuretic peptide level were assessed. Mean age was 62.7±14.3 years. Baseline RVEF was 30.7%±6.3% and baseline LVEF was 21.7%±9.4%. Mean bisoprolol dose reached was 5.3±3.9 mg daily. At 4 months, RVEF significantly increased by 7.1 % (95% confidence interval, 3.9,10.2; p=0.0001) and LVEF also increased significantly by 7.9% (95% confidence interval, 4.0%,11.9%p=0.0003). Quality-of-life score improved from 42.8 to 30.8 (p=0.047). No correlation was found between brain natriuretic peptide levels and RVEF. Bisoprolol treatment for 4 months resulted in a significant improvement of RVEF, which paralleled the improvement of LVEF. [source] Cardiac natriuretic peptides and continuously monitored atrial pressures during chronic rapid pacing in pigsACTA PHYSIOLOGICA, Issue 2 2000Changes in atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide and brain natriuretic peptide (BNP) were evaluated in relation to continuously monitored atrial pressures in a pacing model of heart failure. Pigs were subjected to rapid atrial pacing (225 beats min,1) for 3 weeks with adjustments of pacing frequencies if the pigs showed overt signs of cardiac decompensation. Atrial pressures were monitored by a telemetry system with the animals unsedated and freely moving. Left atrial pressure responded stronger and more rapidly to the initiation of pacing and to alterations in the rate of pacing than right atrial pressure. Plasma natriuretic peptide levels were measured by radioimmunoassay and all increased during pacing with BNP exhibiting the largest relative increase (2.9-fold increase relative to sham pigs). Multiple regression analysis with dummy variables was used to evaluate the relative changes in natriuretic peptides and atrial pressures and the strongest correlation was found between BNP and left atrial pressure with R,2=0.81. Termination of pacing resulted in rapid normalization of ANP values in spite of persistent elevations in atrial pressures. This may reflect an increased metabolism or an attenuated secretory response of ANP to atrial stretch with established heart failure. In conclusion, 3 weeks of rapid pacing induced significant increases in atrial pressures and natriuretic peptide levels. All the natriuretic peptides correlated with atrial pressures with BNP appearing as a more sensitive marker of cardiac filling pressures than ANP and N-terminal proatrial natriuretic peptide. [source] Brain natriuretic peptide in the prediction of recurrence of angina pectorisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2004H. Takase Abstract Background, Circulating levels of brain natriuretic peptide (BNP) provide prognostic information for patients with heart failure, but little is known about its prognostic usefulness in patients with stable angina pectoris. We investigated whether BNP could be used as a marker for the prediction of anginal recurrence after successful treatment. Design, Brain natriuretic peptide levels of 77 patients with stable angina pectoris were measured at enrolment and after confirmation of successful treatment (i.e. no anginal attack for at least 6 months: chronic phase) with percutaneous transluminal coronary angioplasty and/or conventional medication. Then, we prospectively followed them up for 25·9 ± 1·4 months, with the endpoint being a recurrence of anginal attacks. Results, An anginal attack recurred in seven patients. In patients without recurrence, BNP levels in the chronic phase (21 ± 12 [median ± median absolute deviation] pg mL,1) were lower than those measured at enrolment (46 ± 25 pg mL,1, P < 0·0001), whereas the levels in patients with recurrence increased during the same period (from 36 ± 16 to 72 ± 42 pg mL,1, P < 0·05). A univariate analysis revealed that the BNP level measured in the chronic phase was the significant predictor of future anginal recurrence. Analysis of the receiver operating characteristic curve indicated that the cutoff level of BNP in the chronic phase was 68 pg mL,1. The Kaplan-Meier method revealed that the incidence of anginal recurrence was higher in patients with higher (71·4%) than lower levels of BNP (2·9%; P < 0·0001). Conclusions, Measurement of BNP levels after successful therapy is clinically useful for the prediction of recurrence of anginal attacks in patients with angina pectoris. [source] Serum calcitonin gene-related peptide levels in untreated prostate cancer patientsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2006KAZUMI SUZUKI Background:, The role of calcitonin gene-related peptide (CGRP) in prostate cancer has not been fully understood. Moreover, the serum CGRP level in prostate cancer patients has never been reported. We measured the serum CGRP levels in untreated prostate cancer patients to elucidate its clinical significance. Materials and methods:, We used 36 serum samples from prostate cancer patients. All patients had never received any treatment. Serum CGRP was measured by immunoradiometric assay, and we analysed the association between serum CGRP level and clinicopathological factors. Results:, Serum CGRP levels in the patients with higher clinical stages and histological grade were significantly higher than in those with lower stages and grade, respectively. But the levels did not correlate with the patient's age, liver or renal functions, serum prostate-specific antigen levels. Conclusion:, Serum CGRP levels were significantly elevated in the patients with high grade or high stage untreated prostate cancer patients. Measurement of the serum CGRP may be a useful predictor of staging or grading of prostate cancer in the untreated prostate cancer patients. [source] Strong relationship between NT-proXNP levels and cardiac output following cardiac surgery in neonates and infantsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010T. BREUER Background: NT-proXNP, a new natriuretic peptide analyte, incorporates information about the concentrations of both N-terminal pro-atrial and pro-brain natriuretic peptides (NT-proANP, NT-proBNP). We aimed to investigate whether NT-proXNP is a reliable indicator of the cardiac index (CI) and the hemodynamic state in neonates and infants undergoing an open heart surgery. Methods: We enrolled 26 children under the age of 1 year into this prospective study. All patients underwent an elective cardiac operation with cardiopulmonary bypass (CPB) to achieve complete biventricular repair. Peri-operative hemodynamic parameters were assessed by transpulmonary thermodilution and natriuretic peptide levels were recorded. Results: The NT-proXNP level correlated significantly with the simultaneously measured NT-proANP level (r=0.60, P<0.001), but more strongly with the NT-proBNP level (r=0.89, P<0.001) and the arithmetic sum of both (r=0.88, P<0.001). NT-proXNP had a strong correlation with CI (r=,0.85, P<0.001), the stroke volume index (r=,0.80, P<0.001) and the global ejection fraction (r=,0.67, P<0.009) throughout the post-operative period. Conventionally measured parameters such as heart rate, mean arterial pressure and pulse-pressure product exhibited weaker correlations with CI than NT-proXNP. Among laboratory values, creatinine levels correlated significantly with CI (r=,0.77, P<0.001) and NT-proXNP (r=0.76, P<0.001) during the post-operative period. A post-operative NT-proXNP level of 3079 pmol/l was diagnostic for CI <3 l/min/m2 with 89% sensitivity and 90% specificity (area under the curve: 0.91 ± 0.05). Conclusion: NT-proXNP is a good marker of cardiac output following pediatric cardiac surgery and might be a useful tool in the recognition of a low output state. [source] Novel ,-conotoxins identified by gene sequencing from cone snails native to Hainan, and their sequence diversityJOURNAL OF PEPTIDE SCIENCE, Issue 11 2006Sulan Luo Abstract Conotoxins (CTX) from the venom of marine cone snails (genus Conus) represent large families of proteins, which show a similar precursor organization with surprisingly conserved signal sequence of the precursor peptides, but highly diverse pharmacological activities. By using the conserved sequences found within the genes that encode the ,-conotoxin precursors, a technique based on RT-PCR was used to identify, respectively, two novel peptides (LiC22, LeD2) from the two worm-hunting Conus species Conus lividus, and Conus litteratus, and one novel peptide (TeA21) from the snail-hunting Conus species Conus textile, all native to Hainan in China. The three peptides share an ,4/7 subfamily ,-conotoxins common cysteine pattern (CCX4CX7C, two disulfide bonds), which are competitive antagonists of nicotinic acetylcholine receptor (nAChRs). The cDNA of LiC22N encodes a precursor of 40 residues, including a propeptide of 19 residues and a mature peptide of 21 residues. The cDNA of LeD2N encodes a precursor of 41 residues, including a propeptide of 21 residues and a mature peptide of 16 residues with three additional Gly residues. The cDNA of TeA21N encodes a precursor of 38 residues, including a propeptide of 20 residues and a mature peptide of 17 residues with an additional residue Gly. The additional residue Gly of LeD2N and TeA21N is a prerequisite for the amidation of the preceding C -terminal Cys. All three sequences are processed at the common signal site -X-Arg- immediately before the mature peptide sequences. The properties of the ,4/7 conotoxins known so far were discussed in detail. Phylogenetic analysis of the new conotoxins in the present study and the published homologue of ,4/7 conotoxins from the other Conus species were performed systematically. Patterns of sequence divergence for the three regions of signal, proregion, and mature peptides, both nucleotide acids and residue substitutions in DNA and peptide levels, as well as Cys codon usage were analyzed, which suggest how these separate branches originated. Percent identities of the DNA and amino acid sequences of the signal region exhibited high conservation, whereas the sequences of the mature peptides ranged from almost identical to highly divergent between inter- and intra-species. Notably, the diversity of the proregion was also high, with an intermediate percentage of divergence between that observed in the signal and in the toxin regions. The data presented are new and are of importance, and should attract the interest of researchers in this field. The elucidated cDNAs of these toxins will facilitate a better understanding of the relationship of their structure and function, as well as the process of their evolutionary relationships. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd. [source] Period 2 Gene Deletion Abolishes ,-Endorphin Neuronal Response to EthanolALCOHOLISM, Issue 9 2010Maria Agapito Background:, Ethanol exposure during early life has been shown to permanently alter the circadian expression of clock regulatory genes and the ,-endorphin precursor proopiomelanocortin (POMC) gene in the hypothalamus. Ethanol also alters the stress- and immune-regulatory functions of ,-endorphin neurons in laboratory rodents. Our aim was to determine whether the circadian clock regulatory Per2 gene modulates the action of ethanol on ,-endorphin neurons in mice. Methods:,Per2 mutant (mPer2Brdml) and wild type (C57BL/6J) mice were used to determine the effect of Per2 mutation on ethanol-regulated ,-endorphin neuronal activity during neonatal period using an in vitro mediobasal hypothalamic (MBH) cell culture model and an in vivo milk formula feeding animal model. The ,-endorphin neuronal activity following acute and chronic ethanol treatments was evaluated by measuring the peptide released from cultured cells or peptide levels in the MBH tissues, using enzyme-linked immunosorbent assay (ELISA). Results:,Per2 mutant mice showed a higher basal level of ,-endorphin release from cultured MBH cells and a moderate increase in the peptide content in the MBH in comparison with control mice. However, unlike wild type mice, Per2 mutant mice showed no stimulatory or inhibitory ,-endorphin-secretory responses to acute and chronic ethanol challenges in vitro. Furthermore, Per2 mutant mice, but not wild type mice, failed to show the stimulatory and inhibitory responses of MBH ,-endorphin levels to acute and chronic ethanol challenges in vivo. Conclusions:, These results suggest for the first time that the Per2 gene may be critically involved in regulating ,-endorphin neuronal function. Furthermore, the data revealed an involvement of the Per2 gene in regulating ,-endorphin neuronal responses to ethanol. [source] Effect of Ethanol on Hypothalamic Opioid Peptides, Enkephalin, and Dynorphin: Relationship With Circulating TriglyceridesALCOHOLISM, Issue 2 2007Guo-Qing Chang Background: Recent evidence has demonstrated that ethanol intake can stimulate the expression and production of the feeding-stimulatory peptide, galanin (GAL), in the hypothalamic paraventricular nucleus (PVN), and that PVN injection of this peptide, in turn, can increase the consumption of ethanol. To test the hypothesis that other feeding-related systems are involved in ethanol intake, this study examined the effect of ethanol on the hypothalamic opioid peptides, enkephalin (ENK), and dynorphin (DYN). Method: Adult, male Sprague,Dawley rats were trained to voluntarily drink increasing concentrations of ethanol, up to 9% v/v, on a 12-hour access schedule or were given a single injection of ethanol (10% v/v) versus saline vehicle. The effect of ethanol on GAL, ENK, and DYN mRNA was measured using real-time quantitative polymerase chain reaction and radiolabeled in situ hybridization, while radioimmunoassay was used to measure peptide levels. In addition to blood alcohol, circulating levels of triglycerides (TG), leptin, and insulin were also measured. Results: The data demonstrated that: (1) rats voluntarily drinking 9% v/v ethanol (approximately 2.0 g/kg/d) show a significant increase in GAL, ENK, and DYN mRNA in the PVN compared with water-drinking rats; (2) voluntary consumption of ethanol also increases peptide levels of ENK and DYN in the PVN; (3) acute injection of 10% ethanol (1.0 g/kg of 10% v/v) similarly increases the expression of GAL, ENK, and DYN in the PVN; and (4) ethanol consumption and injection, while having little effect on leptin and insulin, consistently increase circulating levels of TG as well as alcohol, both of which are strongly, positively correlated with peptide expression in the PVN. Conclusions: These findings, together with published studies, suggest a possible role for hypothalamic opioid peptides in the drinking of ethanol. Based on evidence that dietary fat and lipid injections stimulate the PVN peptides and injection of the opiates and GAL increase ethanol intake, it is proposed that both TG and alcohol in the circulation, which are elevated by the ingestion or injection of ethanol, are involved in stimulating these peptides in the PVN, which in turn promote further consumption of ethanol. [source] Chronic Ethanol Administration Alters Immunoreactivity for GABAA Receptor Subunits in Rat Cortex in a Region-Specific MannerALCOHOLISM, Issue 8 2000A. Chistina Grobin Background: Chronic ethanol administration has a plethora of physiological effects. Among the most consistently observed findings is a change in the expression pattern of ,-aminobutyric acid type A (GABAA) receptor subunits in the rat brain cortex. These findings led to the hypothesis of "subunit substitution" to account for changes in receptor function without changes in receptor number. Methods: We used subunit (,1 and ,4) specific antibodies and a combination of immunohistochemistry and immunoblotting to examine subregions of cortex (prefrontal, cingulate, motor, parietal, and piriform) for their response to 2 weeks of forced ethanol administration. Results: Overall, cortical immunoreactivity for the ,1 subunit was decreased and for the ,4 subunit increased whether measured immunohistochemically or by immunoblotting. Piriform cortex exhibited a bidirectional change in GABAA receptor ,1 and ,4 immunoreactivity, similar to that previously observed in preparations of whole cortex. However, in parietal cortex, declines in ,1 immunoreactivity (55 ± 12% control value [CV] and 88.3 ± 4.3% CV; immunohistochemistry and immunoblotting, respectively) were not accompanied by concomitant increases in ,4 immunoreactivity (104 ± 8% CV and 116 ± 9.3% CV; immunohistochemistry and immunoblotting, respectively). Conversely, ,4 immunoreactivity increased in cingulate cortex (210 ± 30% CV and 134 ± 9.5% CV; immunohistochemistry and immunoblotting, respectively) without a decline in ,1 immunoreactivity (90 ± 4% CV and 91.3 ± 3.9% CV; immunohistochemistry and immunoblotting, respectively). Prefrontal and motor cortex exhibited GABAA receptor subunit peptide alterations, but these changes varied with the method of analysis. Conclusions: These findings demonstrate that ethanol dependence results in nonuniform changes in GABAA receptor subunit peptide levels across the rat brain cortex and suggest that mechanisms which subserve functional changes in receptor activity may vary in accordance with anatomic or cellular differences within the cortex. [source] Two daytime icodextrin exchanges decrease brain natriuretic peptide levels and improve cardiac functions in continuous ambulatory peritoneal dialysis patientsNEPHROLOGY, Issue 3 2010TANSU SAV ABSTRACT Aim: Peritoneal dialysis patients with ultrafiltration failure frequently have fluid overload. It is known that the increase in the ultrafiltration is associated with decrease in the left ventricle (LV) dysfunction. This study was designed to examine the potential effects of serum brain natriuretic peptide (BNP) on cardiac functions and to determine the relationship between BNP and cardiac parameters in continuous ambulatory peritoneal dialysis (CAPD) patients with ultrafiltration failure. Methods: Twenty-eight patients with high or high-average membrane permeability as indicated by the peritoneal equilibration test were enrolled and randomized to receive either once or twice daily icodextrin. Serum BNP levels and echocardiographic measurements were evaluated at baseline and at the end of the eighth week. The correlations between the percentage changes of parameters from baseline were also studied. Results: In both groups there was a significant decrease in serum BNP, LV mass, heart rate (HR) and cardiothoracic index (CTI) and an improvement in ejection fraction (all P < 0.05). However, the percentage of change in all these parameters was significantly better in the twice daily compared with once daily group (all P < 0.05). Furthermore, the percentage decrease in BNP was positively correlated with the percentage decrease in HR, LV mass and BP. Conclusion: Twice daily icodextrin treatment might be useful in hypervolaemic CAPD patients for the improvement of cardiac functions. BNP monitoring may be useful to follow up these patients. [source] Search for the Optimal Right Ventricular Pacing Site: Design and Implementation of Three Randomized Multicenter Clinical TrialsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2009GERRY KAYE M.D. Background: The optimal site to permanently pace the right ventricle (RV) has yet to be determined. To address this issue, three randomized prospective multicenter clinical trials are in progress comparing the long-term effects of RV apical versus septal pacing on left ventricular (LV) function. The three trials are Optimize RV Selective Site Pacing Clinical Trial (Optimize RV), Right Ventricular Apical and High Septal Pacing to Preserve Left Ventricular Function (Protect Pace), and Right Ventricular Apical versus Septal Pacing (RASP). Methods: Patients that require frequent or continuous ventricular pacing are randomized to RV apical or septal pacing. Optimize RV excludes patients with LV ejection fraction <40% prior to implantation, whereas the other trials include patients regardless of baseline LV systolic function. The RV septal lead is positioned in the mid-septum in Optimize RV, the high septum in Protect Pace, and the mid-septal inflow tract in RASP. Lead position is confirmed by fluoroscopy in two planes and adjudicated by a blinded panel. The combined trials will follow approximately 800 patients for up to 3 years. Results: The primary outcome in each trial is LV ejection fraction evaluated by radionuclide ventriculography or echocardiography. Secondary outcomes include echo-based measurements of ventricular/atrial remodeling, 6-minute hall walk distance, brain natriuretic peptide levels, and clinical events (atrial tachyarrhythmias, heart failure, stroke, or death). Conclusion: These selective site ventricular pacing trials should provide evidence of the importance of RV pacing site in the long-term preservation of LV function in patients that require ventricular pacing and help to clarify the optimal RV pacing site. [source] Diagnostic value of pleural fluid N-terminal pro-brain natriuretic peptide levels in patients with cardiovascular diseasesRESPIROLOGY, Issue 1 2008Huai LIAO Background and objective: The diagnosis of the cause of pleural effusions caused by cardiovascular diseases such as congestive heart failure (CHF) and acute pulmonary embolism is sometimes difficult. The purpose of the present study was to evaluate the utility of pleural fluid levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in differentiating pleural effusions due to CHF, pulmonary embolism and post-coronary artery bypass graft (CABG) surgery. Methods: The levels of pleural fluid NT-proBNP were measured by ELISA in a total of 40 patients: 10 with CHF, 10 with pulmonary embolism, 10 post-CABG and 10 with carcinoma. Results: The median level of NT-proBNP in the pleural fluid of patients with CHF was 5390 pg/mL (25th to 75th percentiles, 4566 to 8158 pg/mL), which was significantly higher than that in patients with post-CABG effusions (424 pg/mL, 352 to 873), with pulmonary embolism (311 pg/mL, 212 to 1159), or with carcinoma (302 pg/mL, 208 to 626) (P < 0.001, CHF group vs all other groups). In receiver-operating curve analysis, an NT-proBNP level of ,2220 pg/mL demonstrated a sensitivity of 100% and a specificity of 96.7% for the identification of CHF. Conclusions: Measurement of the NT-proBNP level in pleural fluid is accurate in diagnosing the etiology of the effusion as CHF. Pleural fluid levels above 2220 pg/mL are essentially diagnostic that the pleural effusion is due to CHF. [source] Serum progastrin-releasing peptide levels followed by whole-body positron emission tomography detects early recurrence of small-cell lung cancerRESPIROLOGY, Issue 1 2007Hiroyuki YAMAGUCHI Abstract: A 65-year-old male smoker with severe COPD was diagnosed with limited-stage small-cell lung cancer. After receiving cisplatin/irinotecan, serum progastrin-releasing peptide (ProGRP) levels decreased to within the reference values and the lesions were markedly reduced in size. A whole-body 18F-fluorodeoxyglucose PET (FDG-PET) scan confirmed complete remission. During follow up, serum ProGRP levels increased, and a whole-body FDG-PET scan detected recurrence at the hilar lymph node that had been negative on CT. Complete remission was again achieved with second-line chemotherapy (cisplatin/etoposide) and local irradiation to the hilar lymph node. Monitoring serum ProGRP levels, followed by whole-body FDG-PET when indicated, may improve the clinical management of patients with small-cell lung cancer after initial complete remission. [source] Simvastatin therapy prevents brain trauma-induced increases in ,-amyloid peptide levels,ANNALS OF NEUROLOGY, Issue 3 2009Eric E. Abrahamson PhD Elevations in ,-amyloid peptide (A,) levels after traumatic brain injury (TBI) may confer risk for developing Alzheimer's disease in head trauma patients. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on hippocampal A, burden in a clinically relevant head injury/intervention model using mice expressing human A,. Simvastatin therapy blunted TBI-induced increases in A,, reduced hippocampal tissue damage and microglial activation, and improved behavioral outcome. The ability of statins to reduce post-injury A, load and ameliorate pathological sequelae of brain injury makes them potentially effective in reducing the risk of developing Alzheimer's disease in TBI patients. Ann Neurol 2009;66:407,414 [source] |