Comparison of several Li doped scintillators for measurement of neutron and γ radiation integral quantities.

Five types of scintillators for parallel detection of neutrons and γ were tested for their pulse shape discrimination ability. All detectors are based on 6Li (n,alpha)3H reaction. LiI, ZnS and polystyrene were used as scintillators. Tests were performed at different neutron and γ mixed fields (AmBe, Cf) using a small Hamamatsu photomultiplier and a Picoscope digitizer. A polystyrene-based ZnS + LiF detector was proven to be the most suitable for neutron-γ separation and similar sensitivity for both types of radiation to construct a single device to measure integral quantities neutrons and γ (fluence, ambient dose equivalent) in parallel. The ZnS + LiF detector based on plexiglass, is in principle useable also, but has low sensitivity to γ radiation. The tested Li glass or LiI crystal does not have the ability to separate neutron and γ. With amplitude discrimination it can be used as a neutron detector for a much simpler probe for a Bonner spectrometer.

Biomarkers for the early detection of anthracycline-induced cardiotoxicity: current status.

BACKGROUND: Cardiotoxicity is a well-known and potentially serious complication of anticancer therapy. Anthracycline-based chemotherapy represents the greatest risk. Early detection of cardiotoxicity is crucial for applying preventive and supportive therapeutic strategies. METHODS AND RESULTS: Various methods have been recommended for monitoring of cardiotoxicity. In our conditions, echocardiography and electrocardiography are routinely used. However, this approach shows low sensitivity for the early prediction of cardiomyopathy when the possibilities of appropriate management could still improve the patient's outcome. Recently, biomarkers of cardiac injury have been investigated in the assessment of chemotherapy-induced cardiotoxicity. Cardiospecific biomarkers, such as cardiac troponins, show high diagnostic efficacy in the early subclinical phase of the disease before the clinical onset of cardiomyopathy. Increase in their concentrations correlates with disease severity. As for natriuretic peptides, some studies, including ours, have shown promising results. Definitive evidence of their diagnostic and prognostic role in this context is still lacking and natriuretic peptides have not been routinely used for monitoring of cardiotoxicity in clinical practice. Other perspective biomarkers of cardiotoxicity in oncology are under study, especially heart-type fatty acid-binding protein (H-FABP) and glycogen phosphorylase BB (GPBB). Our studies using GPBB have provided encouraging results. However, the available data are limited and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined. CONCLUSIONS: This review covers the current status of biomarkers for the early detection of anthracycline-induced cardiotoxicity. The authors present in brief, their own experience with multiple biomarkers in the detection of cardiotoxicity.

Nonplanar tertiary amides in rigid chiral tricyclic dilactams. Peptide group distortions and vibrational optical activity.

We investigate amide nonplanarity in vibrational optical activity (VOA) spectra of tricyclic spirodilactams 5,8-diazatricyclo[6,3,0,0(1,5)]undecan-4,9-dione (I) and its 6,6',7,7'-tetradeuterio derivative (II). These rigid molecules constrain amide groups to nonplanar geometries with twisted pyramidal arrangements of bonds to amide nitrogen atoms. We have collected a full range vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra including signals of C-H and C-D stretching vibrations. We report normal-mode analysis and a comparison of calculated to experimental VCD and ROA. The data provide band-to-band assignment and offer a possibility to evaluate roles of constrained nonplanar tertiary amide groups and rigid chiral skeletons. Nonplanarity shows as single-signed VCD and ROA amide I signals, prevailing the couplets expected to arise from the amide-amide interaction. Amide-amide coupling dominates amide II (mainly C'-N stretching, modified in tertiary amides by the absence of a N-H bond) transitions (strong couplet in VCD, no significant ROA) probably due to the close proximity of amide nitrogen atoms. At lower wavenumbers, ROA spectra exhibit another likely manifestation of amide nonplanarity, showing signals of amide V (δ(oop)(N-C) at ~570 cm(-1)) and amide VI (δ(oop)(C'═O) at ~700 cm(-1) and ~650 cm(-1)) vibrations.

Role of ischemia-modified albumin in estimating the extent and scope of cardiac ischemia in patients with ST elevation myocardial infarction.

Ischemia-modified albumin (IMA) is a laboratory biomarker of cardiac ischemia. Our study aims to determine whether IMA can estimate or represent to any degree the extent of myocardial ischemia. We expect that the higher the marker of cardiac necrosis (maximum value after serial measurements) the greater the preceding cardiac ischemia, indicated by IMA in patients diagnosed with STEMI prior to direct percutaneous coronary intervention (PCI). We studied 216 patients indicated for direct PCI with a diagnosis of ST elevation myocardial infarction. Biochemical analysis of IMA was carried out using the albumin cobalt binding (ACB®) test. We also obtained relevant values for markers of myocardial necrosis (CK, CK-MB, cTnT). In all patients, there was an increased level of IMA prior to the procedure (116 ± 16.9 kU/l); also raised were levels of CK (17.32 µkat/l), CK-MB (4.85 µkat/l) and cTnT (2.97 µg/l) taken as the maximum values obtained after serial measurements at 12, 18, and 24 h after the procedure. We observed that there was no significant association between increase in IMA and cTnT (R2 = 0.0068, p = 0.483). This was also the case for CK-MB (R2 = 0.0011, p = 0.637). IMA does not estimate the extent of ischemia in patients with ST elevation myocardial infarction. However, its absence can be used qualitatively to rule out cardiac ischemia.

Interlaboratory study of free monoclonal immunoglobulin light chain quantification.

BACKGROUND: Quantification of monoclonal immunoglobulin free light chains (FLCs) in serum is used increasingly in clinical practice for the diagnosis, prognostic assessment, and treatment monitoring of monoclonal gammopathies. It is used as an adjunct to standard serum protein electrophoresis and immunofixation. However, methods for FLC quantification need further standardization and validation. METHODS: The Czech Myeloma Group and the Czech Society of Clinical Biochemistry have initiated an interlaboratory study where six laboratories collaborating with the primary myeloma treatment centres measured FLC concentrations in 12 serum samples from patients with monoclonal gammopathies. RESULTS: Repeatability of the measurements in five laboratories was calculated based on differences between the results of duplicate measurements. We found that repeatability depended more on the laboratory than on the device used for measurement. CONCLUSIONS: The study revealed several weak points in the methodology, including the need for a uniform sample dilution procedure. Interlaboratory reproducibility was comparable with values achieved in the NEQAS programme. Because the κ/λ ratio cannot be measured with high precision, κ and λ FLC concentrations should be used where possible. Due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become a part of the regular quality control cycle in myeloma centres.

Plasma interleukin-6 level is associated with NT-proBNP level and predicts short- and long-term mortality in patients with acute heart failure.

OBJECTIVES: Interleukin 6 plays an important role in chronic heart failure (HF), but little is known about its involvement in acute decompensated heart failure (ADHF). The aim of our study is to evaluate the prognostic role of interleukin 6 (IL-6) in the patients with ADHF. METHODS: Plasma levels of interleukin IL-6, N-terminal pro brain natriuretic peptide levels, and clinical covariates were measured in 92 patients with ADHF. Survival was followed up to 12 months, and prognostic factors were evaluated. RESULTS: Elevated plasma IL-6 levels were increased in nonsurvivors and were associated with 1-year mortality (p < 0.01). Plasma IL-6 levels were associated with plasma NT-proBNP levels. In multivariate analysis, increased plasma IL-6 and NT-proBNP levels remained strong independent predictors of 1-year mortality. CONCLUSIONS: Plasma IL-6 levels provide important prognostic information in the patients with ADHF. Measurement combining plasma IL-6 and NT-proBNP should serve as a powerful prognostic tool of multimarker strategy in patients with acute decompensated heart failure.

An organometallic route to long helicenes.

Along with the recent progress in the development of advanced synthetic methods, the chemical community has witnessed an increasing interest in promising carbon-rich materials. Among them, helicenes are unique 3D aromatic systems that are inherently chiral and attractive for asymmetric catalysis, chiral recognition and material science. However, there have been only limited attempts at synthesizing long helicenes, which represent challenging targets. Here, we report on an organometallic approach to the derivatives of undecacyclic helicene, which is based on intramolecular [2 + 2 + 2] cycloisomerization of aromatic hexaynes under metal catalysis closing 6 new cycles of a helicene backbone in a single operation. The preparation of nonracemic compounds relied on racemate resolution or diastereoselective synthesis supported by quantum chemical (density functional theory) calculations. The fully aromatic [11]helicene was studied in detail including the measurement and theoretical calculation of its racemization barrier and its organization on the InSb (001) surface by STM. This research provides a strategy for the synthesis of long helical aromatics that inherently comprise 2 possible channels for charge transport: Along a pi-conjugated pathway and across an intramolecularly pi-pi stacked aromatic scaffold.

Use of the biochip microarray system in detection of myocardial injury caused by radiofrequency catheter ablation.

BACKGROUND: In a prospective study, we measured plasma markers of myocardial damage induced by radiofrequency catheter ablation (RFA) with the protein biochip microarray system. METHODS: A total of 32 consecutive patients undergoing RFA for atrioventricular nodal re-entry tachycardia (AVNRT), right atrial flutter (AFL) and atrial fibrillation (AF) were included in the study. Cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), heart-type fatty acid binding protein (hFABP) and glycogen phosphorylase BB (GPBB) were measured using biochip array technology at baseline and 24 h after the procedure. RESULTS: Values for all markers increased 24 h after RFA (cTnI: 0.92+/-0.49 microg/L vs. 0.33+/-0.06 microg/L, p<0.001; CK-MB: 3.79+/-2.04 microg/L vs. 1.85+/-0.55 microg/L, p<0.001; hFABP: 2.82+/-0.95 microg/L vs. 2.00+/-0.95 microg/L, p<0.001; GPBB: 9.07+/-5.83 microg/L vs. 4.70+/-2.50 microg/L, p<0.001). The correlations between plasma marker levels and RFA time were cTnI: r=0.63, p<0.01; CK-MB: r=0.75, p<0.01; hFABP: r=0.55, p<0.05, GPBB: r=0.51, p<0.05; the correlation between RFA time and number of RF applications was significant (r=0.81, p<0.001). Patients with RFA due to AF or flutter had elevated cTnI, CK-MB and hFABP levels compared to patients with AVNRT (cTnI: 1.14+/- 0.49 microg/L vs. 0.59+/-0.25 microg/L, p<0.05; CK-MB: 4.46+/- 2.07 microg/L vs. 2.81+/-1.54 mug/L, p<0.05; hFABP: 3.21+/- 0.98 microg/L vs. 2.25+/-0.54 microg/L, p<0.01). CONCLUSIONS: Myocardial injury induced by RFA can be detected by cTnI, CK-MB, hFABP and GPBB. Plasma cTnI, CK-MB and hFABP levels significantly increased in patients with AFL and AF compared to patients with AVNRT. The increase of cTnI, CK-MB and GPBB levels correlates with the total duration of RFA.

NT-proBNP and echocardiographic parameters in patients with acute heart failure.

AIM: The aim of this study was to analyse the relation between clinical, haemodynamic and X-ray parameters and plasma NT-proBNP level in pts with symptoms of left ventricular dysfunction. METHODS: The plasma NT-proBNP levels, chest x-ray, transthoracic 2-d and Doppler echocardiography were performed at the time of admission in a group of 96 consecutive patients (mean age 68 +/- 11 years) with symptoms of acute heart failure. NT-proBNP levels were assessed with the use of commercial tests (Roche Diagnostics). RESULTS: All patients have significant increase in NT-proBNP (8000 +/- 9000 pg/mL vs. controls 90 +/- 80 pg/mL, p < 0.001). The group of all patients has shown a significant increase in cardiothoracic ratio (CTR, 0.6 +/- 0.1, vs. 0.4 +/- 0.1, p < 0.001), left atrium diameter (LAD, 4.4 +/- 0.8 cm, vs.3.5 +/- 0.4 cm, p < 0.01). Left ventricular ejection fraction (LVEF) was decreased (37 +/- 15%, vs. 64 +/- 5%, p < 0.001). In patients with acute heart failure, NT-proBNP significantly correlated with end-systolic and end-diastolic left ventricle diameters, ejection fraction, vena cava inferior diameter and plasma creatinine levels. CONCLUSION: Increased plasma NT-proBNP level is influenced by the clinical severity of acute heart failure and correlates with LVEF and IVCD. NT-proBNP can serve as a marker for the clinical severity of the disease.

Monoclonal gammopathies in a series of 1743 plasma donors.

We carried out a retrospective analysis on a series of 1743 plasma donors during the period from January 1999 to February 2004 to determine the frequency of monoclonal gammopathies occurrence. In the whole group, we observed 0.68% occurence and in the subgroup of donors over 40 years of age even 1.18% occurrence of the serum paraprotein. We have presented our recommendations for the screening of monoclonal gammopathies in blood donors.

Prognostic significance of ischemia modified albumin after percutaneous coronary intervention.

UNLABELLED: Ischemia modified albumin (IMA) is a new biochemical marker of ischemia. IMA levels rise in patients who develop ischemia during percutaneous coronary intervention (PCI). It is unclear whether IMA elevations correlate with PCI variables. The possible prognostic value of post-PCI IMA elevation has not yet to be studied. METHODS: We studied 60 patients (mean age 61 years; 51 male) who underwent successful elective single-vessel PCI for the management of stable angina pectoris. IMA levels were measured and compared with PCI variables and target lesion revascularization rate. The median post-PCI follow up is 46 months (CI 44.6 to 47.7). RESULTS: We found that the only variable related to post-PCI IMA levels was periprocedural dissection of target vessel (147.6 vs. 141.1 kU/l, p=0.035). No correlation between high and low balloon inflation pressure (143.6 vs. 141.6 kU/l, p=0.64), short and long inflation pressure (141.5 vs. 143.6 kU/l, p=0.17), with and without stent placement (143.7 vs. 141.3 kU/l, p=0.93) was found. IMA level more then 130 kU/l was associated with higher frequency of target lesion revascularization at nearly 4-years follow-up (p=0.026). CONCLUSION: Post-PCI IMA elevation is associated with higher target lesion revascularization.

The influence of sarin on various physiological functions in rats following single or repeated low-level inhalation exposure.

Long-term effects of low doses of highly toxic organophosphorus agent sarin on various hematological and biochemical markers and physiological functions were studied in rats exposed to sarin by inhalation. The results indicate that low-level sarin-exposed rats show long-term increase in studied markers of stress and decrease in synthesis of DNA de novo without the disturbance of the functions of cholinergic nervous system. Moreover, sarin at low doses is able to induce some neurotoxic effects including an increase in the excitability of central nervous system in rats at 3 mo following inhalation exposure. Relatively long-term spatial discrimination impairments in rats exposed to low-level sarin was demonstrated too. Therefore, nerve agents such as sarin seem to be harmful not only at high, clinically symptomatic doses but also at low doses without acute clinical manifestation of overstimulation of cholinergic nervous system because of long-term manifestation of alteration of neurophysiological and neurobehavioral functions in sarin-exposed rats.