Search

Recently, surface enhanced Raman scattering (SERS) has attracted much attention in medical diagnosis applications owing to better detection sensitivity and lower limit of detection (LOD) than colorimetric detection. In this paper, a novel calibration-free SERS-based μPAD with multi-reaction zones for simultaneous quantitative detection of multiple cardiac biomarkers - GPBB, CK-MB and cTnT for early diagnosis and prognosis of acute myocardial infarction (AMI) are presented. Three distinct Raman probes were synthesised, subsequently conjugated with respective detecting antibodies and used as SERS nanotags for cardiac biomarker detection. Using a conventional calibration curve, quantitative simultaneous measurement of multiple cardiac biomarkers on SERS-based μPAD was performed based on the characteristic Raman spectral features of each reporter used in different nanotags. However, a calibration free point-of-care testing device is required for fast screening to rule-in and rule-out AMI patients. Partial least squares predictive models were developed and incorporated into the immunosensing system, to accurately quantify the three unknown cardiac biomarkers levels in serum based on the previously obtained Raman spectral data. This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based μPAD was identified at 8, 10, and 1 pg mL -1 , for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. Therefore, this proof-of-concept technique shows significant potential for highly sensitive quantitative detection of multiplex cardiac biomarkers in human serum to expedite medical decisions for enhanced patient care., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Authors: Frances Conti-Ramsden MBBS Academic Clinical Fellow 1 , Carolyn Gill PhD BRC Research Assistant 1 , Paul T Seed MSc CStat Senior Lecturer in Medical Statistics 1 , Kate Bramham PhD Clinical Senior Lecturer in Nephrology 2, Lucy C Chappell PhD NIHR Research Professor in Obstetrics 1 , Fergus P McCarthy PhD Clinical Senior Lecturer in Obstetrics and Gynaecology 1,3 ., Objectives: To determine whether glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP) concentrations are elevated in pre-eclampsia and superimposed pre-eclampsia (SPE), demonstrating cardiac ischaemia and strain., Study Design: A nested case-control study was performed using samples and clinical data available from a prospective pregnancy cohort. Four groups were selected: healthy pregnant controls (n = 21), pre-eclampsia (n = 19), pre-existing chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20) or with superimposed pre-eclampsia (SPE) (n = 19). Plasma samples were taken at time of disease or the third trimester in controls., Main Outcome Measures: Plasma concentrations of GPBB and BNP., Results: There was no significant difference in GPBB plasma concentrations between controls and pre-eclampsia (geometric mean (GM) [95% CI]: 4.74 [2.54-8.84]ng/mL vs 5.01 [2.58-9.74]ng/mL, p = 0.90)), or between CHT and/or CKD and SPE (GM [95% CI]: 9.49 [4.93-18.25]ng/mL vs 10.24 [5.27-19.92]ng/mL, p = 0.87). BNP plasma concentrations were significantly raised in women with pre-eclampsia compared to controls (GM [95% CI]: 31.83 [20.18-50.22]pg/mL vs 11.33 [7.34-17.51]pg/mL, p = 0.001). Women with CKD, but not CHT, who developed SPE had elevated BNP concentrations. There were no significant differences in BNP concentration between women with comorbidity (CHT and/or CKD) and controls., Conclusions: GPBB has a limited role as a biomarker in hypertensive disorders of pregnancy. BNP concentrations were elevated in pre-eclampsia compared to controls. This suggests cardiac strain at the time of pre-eclampsia. Further studies are needed to examine whether BNP can identify women at increased risk of cardiovascular disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Glycogen phosphorylase is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to restore depleted energy stores during cerebral ischaemia. We sought to determine whether plasma levels of glycogen phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke (AIS)., Methods: We studied plasma GPBB levels within 12 hours and again at 48±24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133 stroke-free individuals. We determined the ability of plasma GPBB to discriminate between cases and controls and examined the predictive value of plasma GPBB for 90-day functional outcome, 90-day survival and acute lesion volumes on neuroimaging., Results: The mean (SD) GPBB levels were higher in cases (46.3±38.6 ng/mL at first measurement and 38.6±36.5 ng/mL at second measurement) than in controls (4.1±7.6 ng/mL, p<0.01 for both). The area under the receiver operating characteristic (ROC) curve for case-control discrimination based on first GPBB measurement was 0.96 (95% CI 0.93 to 0.98). The sensitivity and specificity based on optimal operating point on the ROC curve (7.0 ng/mL) were both 93%. GPBB levels increased in 90% of patients with punctate infarcts (<1.5 mL) and in all patients admitted within the first 4.5 hours of onset. There was no correlation between GPBB concentration and either clinical outcome or acute infarct volume., Conclusion: GPBB demonstrates robust response to acute ischaemia and high sensitivity for small infarcts. If confirmed in more diverse populations that also include stroke mimics, GPBB could find utility as a stand-alone marker for acute brain ischaemia., Competing Interests: Competing interests: KYP was supported by the Basic Science Research Program through the National Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0023596). IA was supported by NIH grants 1OT2OD023867 and HHSN268201400044C and received research support from Electrocore. OMPN was funded by CNPq grants 402388/2013-5 and 467322/2014-7 and received speaker fees from Boehringer-Ingelheim and Medtronic. NSR received personal compensation for activities with Genzyme, Omniox, Broadview Ventures and CardioNet as a consultant, and Merck for serving on the clinical events committee. NSR received personal compensation in an editorial capacity for Current Treatment Options in Cardiovascular Disease and as a section contributor for UpToDate. NSR is funded by NINDS R01NS086905 and R01NS082285. KLF is a contributing author of UpToDate, Vice Editor of Stroke, Deputy Editor of JNNP, Pfizer DSMB, NINDS research grant P50 NS051343. AGS was an employee of Siemens until January 2016, serves on the board of IMRIS, and has acted as a consultant for Konica Minolta, Permira, EQT Partners, GLG, Third Bridge and Guidepoint in 2016 and 2017. HA received personal compensation as a contributing author of UpToDate., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose of the Study: Heat shock proteins (Hsp) are evolutionary conserved molecules with a chaperone role in cell survival. We hypothesized that cord blood concentrations of molecules reflecting fetal cardiac muscle insult, including Hsp, troponins cTnI and cTnT, and glycol-phosphorylase BB (GP-BB) would be elevated in pregnancies complicated by gestational diabetes (GDM) or preeclampsia (PIH) compared to healthy controls., Materials and Methods: Pregnant women admitted for delivery at >28 weeks were divided into four groups: healthy patients delivered vaginally (VAG), healthy patients delivered by c-section (CS), patients with PIH, and patients with GDM. Demographics, clinical characteristics, and cord blood concentrations of Hsp, troponins cTnI and cTnT, and GP-BB were compared between groups. Statistical analyses included t-test, Chi square, and Wilcoxon rank sum as appropriate., Results: cTnI concentrations were significantly higher in the PIH group compared to the GDM and VAG groups and they were higher in the CS group compared to the VAG group. Concentrations of Hsp70 were higher in the GDM group compared to the VAG and CS groups. Concentration of GP-BB was higher in the PIH group compared to the VAG group., Conclusions: GP-BB and cTNI are the most sensitive markers for PIH-related fetal myocyte injury as is Hsp70 in pregnancies complicated by GDM.

Objectives: To investigate whether maternal plasma glycogen phosphorylase BB (GPBB) levels were altered in early pregnancy and/or at the time of diagnosis of disease in preeclampsia (term and preterm <37 weeks' gestation) or small for gestational age (SGA)., Methods: We conducted 6 nested case-control studies within the Screening of Pregnancy Endpoint (SCOPE) Ireland cohort. Blood samples from women with preeclampsia or SGA were analyzed both from the time of disease presentation and at 15 and 20 weeks' gestation. These were compared with control samples obtained from SCOPE women with healthy uncomplicated pregnancies matched for age, ethnicity, parity, body mass index, and gestational age. Glycogen phosphorylase BB levels were measured using the Diacordon GPBB enzyme-linked immunosorbent assay (Diagenics, Germany)., Results: Glycogen phosphorylase BB levels were higher in women with preeclampsia compared with controls at the time of disease (term preeclampsia median [interquartile range (IQR)]: 22.2 [15.1-39.8] ng/mL vs 16.9 [10.4-19.1] ng/mL; P = .04; N = 14 and preterm preeclampsia median [IQR]: 23.1 [11.2-30.9] ng/mL vs 17.2 [9.8-19.1] ng/mL; P = .04; N = 11) and at 20 weeks' gestation (median [IQR]: 23.0 [15.6-31.4] ng/mL vs 17.0 [13.4-23.6] ng/mL; N = 39; P = .04). Glycogen phosphorylase BB levels were also significantly higher in women with SGA compared with normal controls at the time of disease detection (median [IQR]: 22.7 [12.6-25.5] ng/mL vs 17.0 [9.8-18.0] ng/mL; N = 23; P = .03) but significantly less than controls at 15 weeks' gestation prior to disease detection (median [IQR]: 16.0 [12.1-23.2] ng/mL vs 22.2 [17.0-28.9] ng/mL; N = 25; P = .02)., Conclusion: Glycogen phosphorylase BB alone has modest predictive abilities for the development of preeclampsia or SGA. Further research may examine its use in combination with other markers., (© The Author(s) 2015.)

Background: Transjugular intrahepatic portosystemic shunts (TIPS) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess glycogen phosphorylase BB (GPBB) concentration in relation to echocardiographic and haemodynamic parameters in patients before and after TIPS insertion., Methods: The study population consisted of 55 patients (38 men and 17 women, age 55.6±8.9 years, range 37-74 years) with liver cirrhosis treated with transjugular portosystemic shunting. GPBB, echocardiographic, and haemodynamic parameters were measured before TIPS insertion and 24 h after the procedure. GPBB concentrations were assessed using the Cardiac Array for Evidence Investigator protein biochip. Correlation between parameters was assessed using the Spearman's coefficient., Results: Serum post-procedural GPBB concentrations were increased in comparison with baseline (5.58 vs. 2.67 μg/L, P<0.001). GPBB concentration after TIPS significantly correlated with baseline systemic vascular resistence (r=0.330; P=0.017) and cardiac index (r=0.313; P=0.025)., Conclusion: GPBB concentration measurement may be a useful tool for monitoring myocardial ischemia during a TIPS procedure.

Aim: The glycogen phosphorylase isoenzyme BB (GPBB), as an ischemic marker, has not yet been investigated after elective percutaneous coronary intervention (PCI). ose aim of the study was to monitor GPBB, creatine kinase myocardial isoform (CK-MB) mass) and troponin I (TnI) value after PCI in correlation with ischemic incidents., Methods: Forty-two consecutive patients undergoing elective PCI were included in the study. Baseline blood samples and two more after the PCI (3 and 24 hours) were taken. The significance of cardiac markers in twenty-ththe stable patients with baseline values of CK-MB mass and TnI below the upper reference limit (URL) was evaluated based on ischemic incidents after PCI., Results: TnI value was the only biomarker that was statistically significant at 3 and 24 hours after PCI in group of 23 stable patients. An overall comparisonthe biomarkers of 18 patients without and five patients with ischemic incidents displayed significant differences only for the baseline GPBB (p=0.019) and CK-MB mass 24 hours after PCI (p=0.034). Ischemic incidents were independently predictable only based on overall CK-MB mass measurements (OR=1.680, p=0.041) and particularly GPBB at baseline (OR=1.899, p=0.008) and CK-MB mass 24 hours after PCI (OR=2.111, p=0.022)., Conclusions: Only significant increases in TnI were observed after elective PCI with ischemic incidents predicted using GPBB and CK-MB mass measurements.

Background: Glycogen phosphorylase BB (GPBB) is released from cardiac cells during myocyte damage. Previous studies have shown contradictory results regarding the relation of enzyme release and reversible myocardial ischemia. The aim of this study was to determine the plasma kinetics of GPBB as a response to the exercise stress echocardiographic test (ESET), and to define the relationship between myocardial ischemia and enzyme plasma concentrations., Methods: We studied 46 consecutive patients undergoing ESET, with recent coronary angiography. In all patients, a submaximal stress echo test according to Bruce protocol was performed. Concentration of GPBB was measured in peripheral blood that was sampled 5 min before and 10, 30 and 60 min after ESET., Results: There was significant increase of GPBB concentration after the test (p=0.021). Significant increase was detected 30 min (34.9% increase, p=0.021) and 60 min (34.5% increase, p=0.016) after ESET. There was no significant effect of myocardial ischemia on GPBB concentrations (p=0.126), and no significant interaction between sampling intervals and myocardial ischemia, suggesting a similar release profile of GPBB in ischemic and non-ischemic conditions (p=0.558). Patients in whom ESET was terminated later (stages 4 or 5 of standard Bruce protocol; n=13) had higher GPBB concentrations than patients who terminated ESET earlier (stages 1, 2 or 3; n=33) (p=0.049). Baseline GPBB concentration was not correlated to any of the patients' demographic, clinical and hemodynamic characteristics., Conclusions: GPBB plasma concentration increases after ESET, and it is not related to inducible myocardial ischemia. However, it seems that GPBB release during ESET might be related to exercise load/duration.

Objectives: The aim of the presented study was to assess plasma glycogen phosphorylase BB (GPBB) concentrations in acute leukemia patients treated with anthracycline containing chemotherapy., Background: Anthracyclines represent the highest risk for development of cardiotoxicity. GPBB belongs to proposed biomarkers of cardiac injury with a very limited experience in this context., Methods: Totally, 24 adult patients with acute leukemia were enrolled. Plasma GPBB concentrations were measured by ELISA at diagnosis (before chemotherapy), after first chemotherapy with anthracyclines and 6 months after the completion of treatment. The cut-off value for GPBB positivity was 10.00 µg/L as recommended by the manufacturer., Results: Before chemotherapy, the mean plasma GPBB concentration was 5.25±3.81 µg/L, increased above the cut-off in 1 patient (4.2 %). After the first chemotherapy, the mean GPBB was 6.61±5.54 µg/L, positive in 7 (29.2 %) patients. Six months after treatment, the mean GPBB was 10.06±11.41 µg/L, positive in 8 (33.3 %) patients. Six months after treatment, we found a significant correlation between elevation in GPBB and diastolic left ventricular dysfunction on echocardiography (r=0.621; p<0.0001). The differences in plasma GPBB between healthy blood donors and patients treated for acute leukemia were statistically significant (p<0.01 in all cases)., Conclusion: Our results suggested that GPBB could become a potential biomarker for detection of acute and chronic cardiotoxicity associated with anthracycline containing chemotherapy. The predictive value for development of treatment-related cardiomyopathy in future is not clear and will be evaluated during the follow-up. Further studies are needed to define the potential role of GPBB and other biomarkers in the assessment of chemotherapy-induced cardiotoxicity (Ref. 21). Text in PDF www.elis.sk.

Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from 6 groups (n=396) were studied: nonpregnant and pregnant women with normal term delivery, term and preterm preeclampsia, and term and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term delivery were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in nonpregnant women (38.7 versus 9.2 ng/mL; P<0.001), which remained significant after adjusting for age, race, and parity. Maternal plasma GPBB concentrations did not change throughout gestation. Cases of preterm (but not term) preeclampsia had higher median plasma GPBB concentrations than gestational age-matched normal pregnancy cases (72.6 versus 26.0 ng/mL; P=0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases (P<0.01). There is physiological elevation of plasma GPBB concentration during pregnancy; an increase in maternal plasma GPBB is a novel phenotype of preterm preeclampsia. It is strongly suggested that these changes are attributed to GPBB of placental origin.

Objective: To examine the diagnostic performance of glycogen-phosphorylase-isoenzyme-BB (GPBB) combined with cardiac troponin I (cTnI) in acute coronary syndrome (ACS)., Design and Methods: Sixty patients with chest pain were investigated; GPBB and cTnI were measured., Results: ACS was confirmed in 31 patients; cTnI was >0.07 μg/L in 15 patients and GPBB was >10 μg/L in 6 patients. Areas under ROC curves were similar: 0.854 (cTnI+GPBB) vs. 0.843 (cTnI), p=0.728., Conclusion: Combination of GPBB with cTnI does not improve the detection of ACS., (Copyright © 2011 2011">The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Diabetes mellitus is a syndrome characterized by the loss of glucose homeostasis due to several reasons. In spite of the presence of known anti-diabetic medicines in the pharmaceutical market, remedies from natural resources are used with success to treat this disease. The present study was undertaken to investigate the effect of coconut kernel protein (CKP) on alloxan induced diabetes in Sprague-Dawley rats. Diabetes was induced by injecting a single dose of alloxan (150mg/kg body weight) intraperitoneally. After inducing diabetes, purified CKP isolated from dried coconut kernel was administered to rats along with a semi synthetic diet for 45 days. After the experimental period, serum glucose, insulin, activities of different key enzymes involved in glucose metabolism, liver glycogen levels and the histopathology of the pancreas were evaluated. The amount of individual amino acids of CKP was also determined using HPLC. Results showed that CKP has significant amount of arginine. CKP feeding attenuated the increase in the glucose and insulin levels in diabetic rats. Glycogen levels in the liver and the activities of carbohydrate metabolizing enzymes in the serum of treated diabetic rats were reverted back to the normal levels compared to that of control. Histopathology revealed that CKP feeding reduced the diabetes related pancreatic damage in treated rats compared to the control. These results clearly demonstrated the potent anti-diabetic activity of CKP which may be probably due to its effect on pancreatic β cell regeneration through arginine., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Prolonged strenuous exercise is associated with the appearance of biomarkers of cardiac cell damage and a decline in cardiac function during recovery. Few studies have assessed repeated bouts of prolonged exercise and whether this results in further biomarker accumulation and greater dysfunction. Further, it may be useful to describe the changes in a range of biomarkers that may provide additional insight into the clinical significance of cardiac biomarker release. Four highly trained cyclists completed the 4800 km Race Across America (RAAM) in 7 days. Venous blood samples and echocardiograms were taken prior to, every 24 hours during and immediately after the RAAM. Venous blood was analysed for cardiac troponin I (cTnI), creatine kinase MB (CK-MB), fatty acid binding protein (HFABP), glycogen phosphorylase BB (GPBB) and N-Terminal Brain Natriuretic Peptide (NTproBNP). Echocardiograms allowed analysis of septal, left ventricular free wall and right ventricular free wall tissue velocities during systole and diastole. Before the RAAM cTnI levels were below the assay detection level (0.02 ng.ml⁻¹). In three riders cTnI peaked on day one (0.03 ng.ml⁻¹) and returned below detection levels post race. In the 4th rider cTnI peaked on day 5 (0.08 ng.ml⁻¹) and was still elevated post-race. Both CK-MB and H-FABP were increased during the RAAM in all 4 cyclists. In three riders H-FABP peaked on day one (3.49 to 5.09 ng.ml⁻¹) and declined over the rest of the RAAM. In the final rider H-FABP peaked on day two (5.90 ng.ml⁻¹) and then dropped back to baseline by the post-RAAM assessment. Interestingly, changes in H-FABP mirrored, temporally, changes in CK-MB in places and this may reflect an association with skeletal muscle damage. Data for GPBB value to (2.9 - 149.6 ng.ml⁻¹) and NTproBNP value to (27.3 - 310.0 ng.L⁻¹) were variable but again was elevated in all riders during the course of the RAAM. Changes in ventricular wall tissue velocities were minor and not cumulative. Peak atrial diastolic tissue velocity in the left ventricular free wall increased (P < 0.05) from 11 to 18 cm.s⁻¹ over the last two race days but this did not significantly impact the ratio of early to late diastolic wall motion. Cardiac biomarkers were elevated during the completion of the RAAM in all 4 cyclist but changes were not cumulative which suggest that the hearts of the cyclists coped well with the extreme cardiac work demanded by this ultra-endurance exercise challenge.

Background: Myocardial infarction (MI) with its complications is one of the most serious challenges in contemporary cardiology. Among biochemical markers of myocardial necrosis, heart-type specific fatty acid binding protein (h-FABP) showed excellent sensitivity and specificity for the early diagnosis of an acute MI. The h-FABP is released rapidly (after 30 min) from the cardiomiocyte to the circulation in response to myocardial injury and may be useful for rapid confirmation or exclusion of MI. In recent years, glycogen phosphorylase BB (GP-BB) also emerged as a promising early specific marker of myocardial necrosis. Rapid, qualitative "point of care" tests (POCT) detecting h-FABP (Cardio Detect med) and GP-BB (Diacordon) have recently become available., Aim: To evaluate and compare qualitative POCTs detecting h-FABP and GP-BB in patients with an acute coronary syndrome (ACS)., Methods: We studied 52 patients with a strong suspicion of ACS with persistent ST-segment elevation and chest pain lasting less than 6 hours. The ultimate diagnosis of ST-segment elevation MI (STEMI) was confirmed in case of a second (6 h after admission) positive quantitative result of a cardiac troponin T (cTnT) test. On admission, POCTs to detect both h-FABP and GP-BB were performed. The study population was divided into two groups, with chest pain lasting 〈 3 h (n = 20) or 4-6 h (n = 32). All patients underwent coronary angiography and angioplasty if indicated. The sensitivity of the analysed biomarkers of myocardial necrosis was calculated., Results: The sensitivity of h-FABP (84%) was superior in comparison to the other biomarkers, GP-BB and cTnT, which had sensitivity of 64% and 50%, respectively. Comparison of typical parameters of the diagnostic value of a test (sensitivity, predictive values and accuracy) in both time periods demonstrated that h-FABP was superior to GP-BB. In particular, sensitivity and accuracy of h-FABP was excellent in the group of patients with chest pain lasting 〈 3 h, with sensitivity of 79% for h-FABP and only 47% for GP-BB. Sensitivity and accuracy of cTnT were significantly lower (32% and 35%, respectively)., Conclusions: The h-FABP seems to be an excellent early biomarker of cardiac necrosis in the group of patients with chest pain lasting 〈 3 h. The GP-BB can be also used as a biomarker of myocardic necrosis, but its sensitivity in the early phase of MI is limited.

Background: Evaluating patients with symptoms suggestive of acute coronary syndrome (ACS) is a time consuming, expensive and problematic process in the emergency department. This study aimed to evaluate the diagnostic and prognostic value of glycogen phosphorylase isoenzyme-BB (GP-BB) in ACS., Methods: A total of 72 patients (mean age 61.8 ± 11.6 years) with ACS were enrolled. The ELISA method for determining GP-BB level was performed and considered positive at 〉 10 ng/mL. Duration of angina, type of ACS, demographic features, myoglobin, creatinine kinase and troponin T (cTnT) were also assessed. The cTnT levels eight hours after pain onset was considered the gold standard test for the diagnosis of myocardial infarction., Results: The most sensitive biomarker at first hour of admission was GP-BB (95.8%). However, the specificity of GP-BB was low (43.7%). Receiver operating characteristics curve analysis of the GP-BB level for predicting myocardial infarction revealed the area under the curve value as 0.82 (SE 0.04; 95% CI 0.78-0.85). Positive treadmill exercise test (60% vs 17%, p = 0.047), coronary artery disease (CAD; 59% vs 19%, p = 0.007), percutaneous coronary intervention (44% vs 27%, p = 0.031) and 30-day mortality and/or readmission (33% vs 5%, p = 0.028) were found to be higher in unstable angina (UA) patients having GP-BB (+)., Conclusions: GP-BB is considerably cardiosensitive at the first hour of admission in patients with ACS, but the specificity of GP-BB is lower and it is elevated in nearly half of the patients with UA. However, in this group, GP-BB predicts significant CAD and the combined end-point of mortality and re-hospitalization.

Aim: Monitoring of cardiotoxicity of conventional and high-dose chemotherapy (HD-CT) with multiple biomarkers of cardiac injury - glycogen phosphorylase BB (GPBB), heart-type fatty acid binding protein (H-FABP), cardiac troponins (cTnT, cTnI), creatine kinase MB (CK-MB mass), myoglobin., Methods: A total of 47 adult acute leukemia patients were studied - 24 patients treated with conventional CT containing anthracyclines (ANT) and 23 patients treated with HD-CT (myeloablative preparative regimen) followed by hematopoietic cell transplantation (HCT). Cardiac biomarkers were assessed prior to treatment (before CT/HD-CT), after first CT with ANT, after last CT with ANT in the first group, after HD-CT and after HCT in the second group. Values above the reference range were considered elevated., Results: Before CT/HD-CT, all biomarkers of cardiac injury were below the cut-offs in all patients. GPBB increased above the cut-off (7.30 microg/L) in 4 (16.7%) patients after first CT and in 5 (20.8%) patients after last CT with ANT. GPBB increased above the cut-off in 5 (21.7%) patients after HD-CT and remained elevated in 5 (21.7%) patients after HCT. CTnI became elevated (above 0.40 microg/L) in 2 (8.3%) patients after first and last CT with ANT. Both patients with cTnI positivity had elevated GPBB. Other tested biomarkers remained below the cut-offs during the study., Conclusion: Our results suggest that GPBB could become a sensitive biomarker for detection of acute cardiotoxicity associated with conventional CT containing ANT and HD-CT followed by HCT. The predictive value for development of cardiomyopathy in the future is not known and should be evaluated during a prospective follow-up. Based on our data, a larger prospective and multicenter study would be most desirable to define the potential role of new circulating biomarkers in the assessment of cardiotoxicity in oncology.

The diagnosis of acute myocardial infarction currently rests on the measurement of troponin, a biomarker of myocardial necrosis. Unfortunately, the current generation troponin assays detect troponin only 6-9 h after symptom onset. This can lead to a delay in diagnosis and also excessive resource utilization when triaging patients who, ultimately, have noncardiac causes of acute chest pain. For these reasons, there has been extensive research interest in biomarkers that can detect and rule out myocardial infarction early after symptom onset. These include markers of myocardial injury, such as myoglobin, heart-type fatty acid binding protein, glycogen phosphorylase BB; hemostatic markers, such as D-dimer; and finally, inflammatory markers, such as matrix metalloproteinase 9. Recently, highly sensitive troponin assays have reported an early sensitivity for myocardial infarction of greater than 95%, although at a cost of reduced specificity. The optimal strategy with which to use these novel biomarkers and highly sensitive troponins has yet to be determined, and interpretation of their results in light of thorough clinical assessment remains essential.

Objective: To investigate the changes and the clinical significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) and glycogen phosphorylase isoenzyme BB (GPBB) levels in neonates with asphyxia complicated by myocardial injury., Methods: Sixty-four neonates with asphyxia (39 mild, 25 severe) were enrolled. Of the 64 neonates, 30 had myocardial injury and 34 did not develop myocardial injury. Twenty-five healthy neonates served as a control group. Plasma levels of NT-proBNP and GPBB were measured using ELISA. Myocardial enzymes and cardiac troponin I were stimultaneously measured, and electrocardiography and chest radiographs were obtained., Results: The plasma levels of NT-proBNP and GPBB in neonates with myocardial injury were significantly higher than those in neonates without myocardial injury and in the control group (P<0.01). The neonates with severe asphyxia had significantly increased plasma NT-proBNP and GPBB concentrations compared to those with mild asphyxia and the control group (P<0.01). Spearman rank correlation analysis showed that plasma NT-proBNP level was positively correlated with plasma GPBB level in neonates with asphyxia. Plasma levels of NT-proBNP and GPBB were also positively correlated with plasma levels of CK-MB, CK and LDH (P<0.01)., Conclusions: Both NT-proBNP and GPBB can be used as biomarkers of myocardial injury in neonates with asphyxia. The measurement of plasma NT-proBNP and GPBB levels was useful in early identification of myocardial injury and severity evaluation in neonates with asphyxia.

The action of glycogen phosphorylase (GP) is essentially reversible, although GP is generally classified as a glycogen-degrading enzyme. In this study, we developed a highly sensitive and convenient assay for GP activity by analysing its chain-lengthening action on a fluorogenic maltooligosaccharide derivative in a glucose-1-phosphate-rich medium. Characterization of the substrate specificity of GP using pyridylaminated (PA-) maltooligosaccharides of various sizes revealed that a maltotetraosyl (Glc(4)) residue comprising the non-reducing-end of a PA-maltooligosaccharide is indispensable for the chain-lengthening action of GP, and PA-maltohexaose is the most suitable substrate for the purpose of this study. By using a high-performance liquid chromatograph equipped with a fluorescence spectrophotometer, PA-maltoheptaose produced by the chain elongation of PA-maltohexaose could be isolated and quantified at 10 fmol. This method was used to measure the GP activities of crude and purified GP preparations, and was demonstrated to have about 1,000 times greater sensitivity than the spectrophotometric orthophosphate assay.

Background: Glycogen Phosphorylase BB (GPBB) is considered an early and specific marker of myocardial necrosis and ischemia. A POCT kit GPBB for diagnostic use has recently been approved., Aim: an evaluation of the correspondence of qualitative POCT GBPP measurements with ELISA test results., Material and Methodology: 20 individuals with non-ST elevation myocardial infarction (non-STEMI) and 20 probands without acute coronary syndrome (ACS) were tested. GPBB (POCT, ELISA) in venous plasma (lithium-heparin) was assayed in all probands., Results: individuals with non-STEMI had significantly higher GPBB ELISA values (32.3 vs. 6.1 microg/l; p < 0.01). GPBB sensitivity and specificity for non-STEMI presence 6 hours after chest pain generation were 100 %. No proband was classified in a different subgroup with POCT of GPBB (positive/negative). GPBB POCT correlate with a non- STEMI diagnosis (chi(2) 36.1; p <0.01)., Conclusion: GPBB POCT measurement is comparable with ELISA test results. GPBB analysis could expand the diagnostic palette in the first hours after the onset of acute coronary syndrome.

Introduction: Glykogen Phosphorylase BB is considered a timely and specific marker of acute coronary syndrome. A kit for measuring Glykogen Phosphorylase BB in routine diagnosis has been released recently., Objective of the Study: To test the utilisation of Glykogen Phosphorylase BB measurement in the diagnosis of acute coronary syndrome., Method: 70 patients with suspected acute coronary syndrome were tested. A final diagnosis of acute coronary syndrome/non-coronary difficulties was made according to ESC/ACC/AHA criteria. Measurements of troponin I, myoglobin and GPBB in venous plasma (heparin-lithium) were taken for all probands on admission and two and six hours later., Results: Individuals with acute coronary syndrome (n = 52) had significantly higher levels of Glykogen Phosphorylase BB on admission and 2 hours after admission (21.9 vs 6.2; 18.7 vs 5.9 microg/l; p < 0.01). Levels of Glykogen Phosphorylase BB had a greater diagnostic effectiveness for the presence of acute coronary syndrome than levels of troponin I (threshold below ROC curve 0.89 vs. 0.78; 0.87 vs. 0.67). In the first two hours after admission, only levels of Glykogen Phosphorylase BB were included as independent variables in the regression model for the incidence of acute coronary syndrome (p < 0.05). When the group of patients with myocardial necrosis (n = 39; acute myocardial infarction without ST elevations on ECG; NSTEMI) is removed from the group with acute coronary syndrome, it was found that only GPBB and cTnl were independent variables in the regression model on initial testing and after two hours. After adjusting GPBB to cTnl, significantly higher levels of GPBB adjusted to troponin I were found in persons with NSTEMI (14.5 vs -48.0; p < 0.01)., Conclusion: Measurement of Glykogen Phosphorylase BB has excellent effectiveness independently of troponin in the first hours after the onset of acute coronary syndrome and should ensure the correct diagnosis of acute coronary syndrome in combination with troponin.

To test the hypothesis that cortisol has a regulatory role in fish muscle glycogenesis post-exercise, rainbow trout were treated 1 h prior to exercise with either saline (control) or metyrapone (2-methyl-1, 2-di-3-pyridyl-1-propanone) to block cortisol synthesis. Following exercise (time 0), half of the metyrapone-treated fish received a single injection of cortisol, to mimic the post-exercise rise usually observed. Muscle glycogen and the relative activities of glycogen phosphorylase a (Phos a) and glycogen synthase I (GSase I), regulatory enzymes for glycogen resynthesis, were monitored 4 h post-exercise. Metyrapone treatment succeeded in blocking the post-exercise rise in plasma cortisol (17+/-2 vs 118+/-13 ng ml(-1) in controls at time 0), and cortisol injection resulted in a larger and more prolonged cortisol increase than in controls (159+/-22 vs 121+/-14 ng ml(-1) in controls at 1 h). Muscle glycogen was completely restored in the metyrapone-treated fish within 2 h after exercise (8.3+/-0.6 vs 8+/-0.7 micromol g(-1) pre-exercise), only partially restored in control fish at 4 h (5.4+/-01.4 vs 8.8+/-1.3 micromol g(-1) pre-exercise), and not at all in cortisol-treated fish (1.0+/-0.5 micromol g(-1) at 4 h). The rapid glycogen resynthesis in the metyrapone-treated fish was associated with a more rapid inactivation of Phos a and stimulation of GSase I compared to controls. In cortisol-treated fish, Phos a activity persisted throughout 4 h post-exercise; there was also a significant stimulation of GSase I activity. As a consequence of dual activation of Phos a and GSase I, glycogen cycling probably occurred, thus preventing net synthesis. This explains why the post-exercise elevation of cortisol inhibits net glycogen synthesis in trout muscle.

Acute coronary syndromes remain the leading cause of mortality in the United States and represent an enormous cost to the health care system. Despite decades of investigation into the diagnosis of acute myocardial infarction (MI), the diagnostic process is still quite complex because the majority of patients with chest pain fall in the low or medium risk category with atypical symptoms and nonspecific electrocardiogram (ECG) changes. Cardiac biochemical markers play an important role in helping physicians make the diagnosis and stratify the risk to patients. However, the ideal cardiac marker and the best diagnostic approach to patients with chest pain in the Emergency Department (ED) remain elusive. Currently, among many cardiac markers, cardiac troponin I seems the most cardiac-specific in the diagnosis of acute MI. This article is focused on reviewing the characteristics of different cardiac markers and comparison of their usages in the diagnosis of acute MI. However, since this field is large and rapidly expanding, it is impossible to cover every aspect of cardiac markers. As the search for the most efficacious, specific and cost-effective means to approach patients with chest pain continues, further prospective, randomized, multicenter trials are needed to confirm the value of troponins and other diagnostic strategies in the early diagnosis of acute MI.